DETAILED ACTION
Applicant’s response filed 5/10/2026 has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-19 are pending and under consideration in this action. Claim 20 was canceled in the amendment filed 5/10/2026.
Priority
The instant application is a 371 of PCT/CN2021/132568, filed 11/23/2021. The instant application does not claim domestic or foreign benefit, as reflected in the filing receipt mailed 2/27/2024. The filing date of the 371 application is the effective filing date of claims 1-19. As such, the effective filing date of claims 1-19 is 11/23/2021.
Claim Objections
Withdrawn Objections
The objection to claim 1 is withdrawn in view of Applicant’s amendments to the claims filed 5/10/2026 (Applicant’s Remarks, Pg. 11).
Newly Recited Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites the limitation “calculating a structural characteristic vector based on the correlation matrix , wherein calculating…” in lines 5-6 of the claim, which should be corrected to “calculating a structural characteristic vector based on the correlation matrix” to remove the additional space before the comma.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
Withdrawn Rejections
The rejection of claims 15-17 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement is withdrawn in view of Applicant’s amendments to the claims filed 5/10/26, and Applicant’s Remarks were found persuasive (Applicant’s Remarks, Pg. 12-14).
The rejection of claims 15-20 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is withdrawn in view of Applicant’s amendments to the claims filed 5/10/26, and Applicant’s Remarks were found persuasive (Applicant’s Remarks, Pg. 15-16).
Maintained Rejections
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
1. Claims 18-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Any newly recited portion of this rejection is necessitated by claim amendment.
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention. The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable?. See also In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation (MPEP § 2164.06).
The specification fails to enable the if a person of ordinary skill in the art would be faced with an undue burden of experimentation when trying to implement the invention based on the disclosure. In re Wands (858 F.2d 731 at 737, 8 USPQ2d 1400 at 1404 (Fed. Cir. 1988)) sets forth a non-exclusive list of factors by which this burden of experimentation may be judged to be due or undue; factors that are germane to the instant case include the breadth of the claims, the state of the prior art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to use the invention based on the content of the disclosure.
Claim 18 recites the limitation “administering a gene expression vector targeting at least one gene located at or near said at least one chromatin locus identified as exhibiting said structural aberration, wherein said gene expression vector modulates expression of said at least one gene”. The specification (Para. [0057]) recites that if the chromatin structural characteristic is indicative of a disease, a gene vector therapy can be administered, which may include the usage of transcription or translation production at a particular locus. The specification broadly recites the administration of a gene vector but does not provide any indication of how the gene therapy vector was determined based on the identified chromatin structural characteristic for any cancer intervention.
Claim 19 recites the limitation “wherein said gene expression vector comprises at least one selected from the group consisting of an overexpression vector, an shRNA expression vector, an siRNA expression vector, a CRISPR activation/inhibition vector, and an antisense expression construct. The specification (see Para. [0056]-[0057]) discloses that treatment may involve usage of transcription or translation production of the obtain loci as a disease target. And that the gene therapy may include usage of transcription of translation production of at least one locus associated with the chromatin structural characteristic in the target cells as a disease target. The specification therefore broadly recites potential therapeutics options but does not recite the application of any of the listed interventions for any type of cancer.
Regarding the administration of a gene therapy, a review on gene therapies for cancer by Das et al. (Gene Therapies for Cancer: Strategies, Challenges and Successes. J Cell Physiol. 230(2): 259-71 (2015); previously cited), highlights that gene therapy success in the clinic requires overcoming numerous hurdles. These include non-specific expression, low-efficiency delivery, and biosafety (Abstract). Das et al. further discloses that the major reasons for failure or limited success of cancer gene therapy are not only technical, but also related to ethical, policy and financial issues. Unlike chemotherapies, gene therapies are only effective in a subset of patients with any given cancer, making each gene therapy agent an orphan drug. Moreover, failure to target metastatic cells, the major driver of cancer-associated mortality has limited the general utility of cancer gene therapy (Pg. 268, Col, 2, Para. 3). Gene therapies, therefore, require significant experimentation to make them effective and safe for a given cancer.
As described above, the instant specification (Para. [0057]) broadly recites that a gene vector therapy can be administered. However, the specification provides no working examples or additional guidance on how the gene vector therapy is determined for any cancer, in order to perform the claimed invention. Additionally, the specification (see Para. [0071]-[0083]) provides examples of how the method can be used to distinguish cancer cells from other cell types. However, the specification does not provide any examples of how a gene vector therapy is administered after the identification of a chromatin locus as a candidate target, as recited in instant claims 18 and 19.
Because the disclosure does not provide a description or examples of how the gene therapy vector is determined for any target, and because gene therapy vectors for any cancer are not readily available within the teachings of the prior art, a person of ordinary skill in the art who wished to practice the invention would have to perform additional experimentation to make and use the claimed invention. Specifically, that person would have to experiment to determine an appropriate gene vector therapy to treat any cancer. Whether or not a gene vector therapy will be effective for any of the claimed cancers cannot be predicted ahead of time, only by actually creating the therapy and testing it. The vast number of gene therapies that could be designed for any of the claimed cancers and the total absence of direction from the inventor regarding how to determine the gene vector therapy results in that burden of experimentation being undue. The claims therefore fail to comply with the enablement requirement of 35 U.S.C. § 112(a).
2. Claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly recited and necessitated by claim amendment.
Claim 19 recites the limitation “wherein said gene expression vector comprises at least one selected from the group consisting of an overexpression vector, an shRNA expression vector, an siRNA expression vector, a CRISPR activation/inhibition vector, and an antisense expression construct”. The specification (see Para. [0056]-[0057]) discloses that the gene therapy may include usage of transcription of translation production of at least one locus associated with the chromatin structural characteristic in the target cells as a disease target. The specification therefore broadly recites potential therapeutics options but does not recite the application of any of the listed vectors for any type of cancer. Accordingly, the disclosure in not commensurate with the written description scope of the claim. This is a new matter rejection.
Response to Arguments under 35 U.S.C. 112(a)
Applicant’s arguments filed 5/10/2026 have been fully considered but they are not persuasive. Examiner notes that the arguments below address the maintained enablement rejection for claims 18-19 and written description rejection for claim 19.
1. Applicant argues that for claim 18, "administering a gene expression vector targeting at least one gene located at or near said at least one chromatin locus ... wherein said gene expression vector modulates expression of said at least one gene" is directly supported by Para [0056]: "In the method of treating a disease, the method includes administering a gene therapy vector to a subject in need thereof...usage of transcription or translation production of at least one locus associated with the chromatin structural characteristic in the target cells as a disease target." Also supported by [0055]: "Treatment may involve the usage of transcription or translation production of the obtained loci as a medical condition or disease target." For claim 19, the specific vector types listed are sub-categories of "gene expression vector" explicitly contemplated by [0055]-[0056]. Once the concept of using a gene expression vector to modulate expression of a target locus is established, enumerating standard vector implementations (overexpression, shRNA, siRNA, CRISPR, antisense) constitutes routine elaboration well-understood by those skilled in the art (Applicant’s Remarks, Pg. 13-14).
It is respectfully submitted that this is not persuasive for the following reasons:
Regarding claim 18, while the specification (see Para. [0055]-[0056]) provides support for the administering step, it is merely reiterating the claim language, as described in the rejection above. Claim 18 recites the administration of a gene expression vector after the identification of a chromatin locus as a candidate target in claim 17. In order to administer the gene expression vector to any subject for any cancer, the gene expression vector would need to be developed. As described by Das et al. above, the development is a complex process, and one that is not described at all by the inventor, resulting in an undue burden of experimentation.
Regarding claim 19, the specification (see Para. [0055]-[0056]) fails to describe any of the recited vector implementations. Das et al. (see Pg. 260, Col. 1, Para. 1 and Pg. 264, Col. 2, Para. 2-3) highlights prospective strategies including antisense, siRNA, and shRNA. Similar to claim 18, administering any of these therapies requires significant development before the administration step. However, the specification fails to provide any guidance or examples for the development and subsequent administration, resulting in the burden of experimentation being undue. This argument is thus not persuasive and the rejection is maintained.
2. Applicant also argues that Das et al. describes clinical hurdles for gene therapy delivery. However, the amended claim 17 does not require administering therapy to a human subject - it only requires identifying a target and outputting its identifier. Claim 18 administers a gene expression vector, but the design and administration of such vectors following target identification is routine pharmaceutical practice. The clinical development hurdles described by Das arise at a later stage and do not bear on whether target identification or vector administration per se is enabled (Applicant’s Remarks, Pg. 15).
It is respectfully submitted that this is not persuasive for the following reasons:
Examiner agrees that amended claim 17 is enabled, as it no longer requires the administration of a gene expression vector. However, claim 18 and 19 require the administration of a gene vector therapy. Under the broadest reasonable interpretation (BRI), the administration step is to a subject, human or otherwise. After the identification of a chromatin locus as a candidate target in claim 17, the gene expression vector still needs to be developed prior to administration recited in claims 18/19. Das et al. discloses the challenges of developing therapies both clinically and in comparison to pre-clinical studies for administration to a human subject (see at least Pg. 268, Col. 1, Para. 2 – Col. 2, Para. 2). While developing a gene therapy is routine pharmaceutical practice, it does not change that the development process requires significant experimentation, as disclosed by Das et al. This argument is thus not persuasive.
3. With regards to written description, Applicant also argues that for claims 16-19 (target identification and gene vector), Paragraphs [0055]-[0056] demonstrate the inventors possessed the full chain of the invention. Section header - "Methods for diagnosing and treating a medical condition or disease." Para [0061]: Atlas used for distinguishing normal/cancer samples; treatment involves usage of transcription or translation production of identified loci; specific genes listed: SPAG9, TOBI, UTP18. [0062]: Explicitly recites "administering a gene therapy vector" and "usage of transcription or translation production" (Applicant’s Remarks, Pg. 16).
It is respectfully submitted that this is not persuasive for the following reasons:
Examiner agrees that amended claims 16-18 comply with the written description requirement. However, claim 19 recites “wherein said gene expression vector comprises at least one selected from the group consisting of an overexpression vector, an shRNA expression vector, an siRNA expression vector, a CRISPR activation/ inhibition vector, and an antisense expression construct”. While the specification (Para. [0056]-[0057]) discloses the usage of transcription or translation production, it does not disclose any of the recited vector therapies. Accordingly, these introduce new matter, and this argument is not persuasive.
Claim Rejections - 35 USC § 112(b)
Withdrawn Rejections
The rejection of claims 15-20 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments to the claims filed 5/10/2026 and Applicant’s Remarks were found persuasive (Applicant’s Remarks, Pg. 16-17).
Newly Recited Rejections
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 14 and 17-19 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.
Claim 14 recites the limitation “a non-transitory computer readable medium storing a program for identifying a chromatin structural characteristic from a Hi-C matrix of claim 1, the program causing a processor to execute: performing a correlation process… calculating a structural characteristic vector…, calculating a principal component fraction matrix…, and identifying at least one chromatin structural characteristic in the principal component fraction matrix” in lines 1-9 of the claim. The metes and bounds of the claim are rendered indefinite due to the lack of clarity. The claim recites a program for identifying a chromatin structural characteristic from a Hi-C matrix of claim 1, which causes a processor to execute the same steps (albeit broader) than those recited in claim 1. It is unclear whether these broader steps are intended to be the same steps recited in claim 1, or if the processor is executing additional analyses using only the Hi-C matrix from in claim 1. Clarification through clearer claim language is respectfully requested.
Claim 17 recites the limitation “identifying at least one chromatin locus exhibiting a structural aberration in said chromatin structural characteristic…” in lines 3-4 of the claim. There is insufficient antecedent basis for said chromatin structural characteristic in the claim, since there is no prior mention of this phrase earlier in the claim. Based on the enablement arguments presented by Applicant (see Pg. 14 of Applicant’s Remarks), it appears the limitation of identifying at least one chromatin locus… is step 2 of the claim. However, as currently amended, this limitation is step 1 of claim 17. It is unclear whether said chromatin structural characteristic is determined using the method of claim 1, analogous to claim 15. This rejection can be overcome by amendment of claim 17 to recite steps to determine said chromatin structural characteristic. Claims 18-19 are also rejected due to their dependency from claim 17.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10, 12, and 13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
This rejection is newly recited and necessitated by claim amendment.
Claim 10 recites the limitations “wherein calculating the principal component fraction matrix from the structural characteristic vector includes: splicing the structural characteristic vector into an input matrix with a defined shape so that each row of the input matrix is a structural eigenvector; normalizing the input matrix; and performing matrix decomposition and dimensionality reduction to obtain a coefficient matrix and the principal component fraction matrix”. Claim 1 recites the limitation “calculating a principal component fraction matrix from the structural characteristic vector by splicing structural characteristic vectors of a plurality of samples into an input matrix, normalizing the input matrix, and performing matrix decomposition and dimensionality reduction”. As currently recited, the steps of splicing structural characteristic vectors, normalizing the input matrix, and performing matrix decomposition and dimensionality reduction recited in claim 10 are already recited in the limitation in claim 1. Therefore, claim 10 fails to further limit the subject matter of amended claim 1.
Claims 12 and 13 recite the limitations “wherein identifying the at least one chromatin structural characteristic in the principal component fraction matrix includes performing geometric visualization” and “wherein the geometric visualization is a visualized cell type atlas”, respectively. Claim 1 recites the limitation “identifying at least one chromatin structural characteristic in the principal component fraction matrix by embedding the principal components into a visualized cell type atlas to distinguish between different cell types”. The process of embedding the principal components into a visualized cell type atlas, as recited in claim 1, is a form of geometric visualization (see also Specification Para. [0024]-[0026] and [0040] and Fig. 7-9, which describe examples of a PCA-derived cell type atlas, which is a form of geometric visualization). Therefore, the geometric visualization and the visualized cell type atlas disclosed in claims 12 and 13 do not further limit the amended claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
Maintained Rejections
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 1-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite both (1) mathematical concepts (mathematical relationships, formulas or equations, or mathematical calculations) and (2) mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
Any newly recited portion is necessitated by claim amendment.
Step 1:
In the instant application, claims 1-13 and 15-19 are directed towards a method and claim 14 is directed towards a manufacture, which falls into one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
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 One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claim 1 recites a mathematical concept (i.e., calculation of a correlation matrix) in “performing a correlation process on the Hi-C matrix to calculate a correlation matrix through a plurality of iterations”; a mathematical concept (i.e., vector calculation) in “calculating a structural characteristic vector based on the correlation matrix, wherein calculating the structural characteristic vector comprises at least one of: (i) calculating different quantiles of the correlation matrix and converting the correlation matrix into a binary logical matrix based on each quantile threshold to obtain a one-dimensional structural characteristic vector at multiple scales defined by the quantiles; and (ii) for each locus, extracting a sub-matrix from the correlation matrix based on a window size centered at the locus, and averaging the sub-matrix into a one-dimensional vector whose length equals a number of chromatin bins”; a mathematical concept (i.e., matrix calculation) in “calculating a principal component fraction matrix from the structural characteristic vector by splicing structural characteristic vectors of a plurality of samples into an input matrix, normalizing the input matrix and performing matrix decomposition and dimensionality reduction”; and a mental process (i.e., an evaluation of the visualized cell type atlas) / mathematical concept (i.e., embedding principal components) in “identifying at least one chromatin structural characteristic in the principal component fraction matrix by embedding the principal components into a visualized cell type atlas to distinguish between different cell types”.
Claim 2 recites a mental process (i.e., an observation of the type of matrix) in “wherein the Hi-C matrix is a raw-data Hi-C matrix”.
Claim 3 recites a mental process (i.e., an observation of the type of matrix) in “wherein the Hi-C matrix is a normalized Hi-C matrix”.
Claim 4 recites a mathematical concept (i.e., correlation calculation) in “wherein the correlation process is at least one process selected from the group consisting of Pearson correlation, Spearman correlation, and cosine similarity”.
Claim 5 recites a mathematical concept (i.e., quantile calculation and similarity calculation) in “wherein calculating the structural characteristic vector based on the correlation matrix includes at least one of calculating a quantile of the correlation matrix and characterizing similarity between a locus and at least one neighbor of the locus”.
Claim 6 recites a mathematical concept (i.e., quantile calculation) in “wherein calculating the structural characteristic vector based on the correlation matrix includes calculating the quantile of the correlation matrix”.
Claim 7 recites a mathematical concept (i.e., binary matrix calculation) in “wherein the correlation matrix is converted into a binary matrix”; and a mathematical concept (i.e., matrix element conversion) in “matrix elements greater than the quantile are converted to 1 or 0 and matrix elements less than the quantile are converted to the other of 1 or 0”.
Claim 8 recites a mathematical concept (i.e., similarity calculation) in “wherein calculating the structural characteristic vector based on the correlation matrix includes characterizing similarity between at least one locus and at least one neighbor of the locus”.
Claim 9 recites a mathematical concept (i.e., average similarity calculation) in “wherein, for each locus, an average similarity between neighbor loci in a window is calculated”; a mathematical concept (i.e., sub-matrix generation) in “a sub-matrix is generated from the correlation matrix based on a size of the window”; and a mathematical calculation (i.e., sub-matrix averaging) in “the sub-matrix is averaged into the structural characteristic vector having a length equal to a number of chromatin bins”.
Claim 10 recites a mathematical concept (i.e., matrix generation) in “splicing the structural characteristic vector into an input matrix with a defined shape so that each row of the input matrix is a structural eigenvector”; a mathematical concept (i.e., matrix normalization) in “normalizing the input matrix”; and a mathematical concept (i.e., dimensionality reduction) in “performing matrix decomposition and dimensionality reduction to obtain a coefficient matrix and the principal component fraction matrix”.
Claim 11 recites a mathematical concept (i.e., dimensionality reduction) in “wherein performing matrix decomposition and dimensionality reduction includes at least one selected from the group consisting of principal component analysis, non-negative matrix decomposition eigenvalue decomposition, and singular value decomposition algorithm”.
Claim 14 recites a mathematical concept (i.e., calculation of a correlation matrix) in “performing a correlation process on the Hi-C matrix to calculate a correlation matrix”; a mathematical concept (i.e., vector calculation) in “calculating a structural characteristic vector based on the correlation matrix”; a mathematical concept (i.e., matrix calculation) in “calculating a principal component fraction matrix from the structural characteristic vector”; and a mental process (i.e., an evaluation of the matrix to determine a chromatin structural characteristic) in “identifying at least one chromatin structural characteristic in the principal component fraction matrix”.
Claim 15 recites a mental process (i.e., an identification of a chromatin structural characteristic as described for claim 1 above) in “identifying the chromatin structural characteristic according to the method of claim 1”; and a mental process (i.e., a comparison with the reference cell type atlas) in “detecting whether a test sample has a chromatin structural abnormality by comparing said chromatin structural characteristic with a reference cell type atlas, wherein said reference cell type atlas is generated from Hi-C matrices of known normal cells and known cancer cells, wherein a chromatin structural characteristic falling within a region occupied by cancer samples in said reference cell type atlas indicates that said test sample has a chromatin structural abnormality associated with cancer”.
Claim 16 recites a mental process (i.e., an evaluation of the type of disease) in “wherein the said cancer is selected from the group consisting of oral cancer, colon cancer, bladder cancer, lung cancer, leukemia, lymphoma, and hematological malignancy”.
Claim 17 recites a mental process (i.e., an identification of a chromatin structural characteristic by comparing a difference between normal and cancer samples) in “identifying at least one chromatin locus exhibiting a structural aberration in said chromatin structural characteristic, wherein said structural aberration is determined by identifying positions in said structural characteristic vector that exhibit a largest difference between normal samples and cancer samples”; and a mental process (i.e., an observation of an output identifier) in “outputting an identifier of said at least one chromatin locus as a candidate target for cancer intervention”.
These recitations are similar to the concepts of collecting information, and displaying certain results of the collection and analysis is Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), and organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Specifically, claim 1 involves nothing more than performing a correlation, calculating a structural characteristic vector, calculating a principal component fraction matrix, and identifying at least one chromatin structural characteristic. The steps reciting performing a correlation, calculating a structural characteristic vector, calculating a principal component fraction matrix are, under the BRI, performed using mathematical operations. The instant Specification (see Para. [0032]) discloses that the correlation matrix is calculated though Pearson correlation, Spearman correlation, and cosine similarity. The instant Specification (see Para. [0034]-[0035]) also discloses that the structural characteristic vector may be derived by calculating different quantiles of the correlation matrix, or that for each locus, the average similarity between each two loci on a window centered around the locus is calculated. The instant Specification (see Para. [0037]) also discloses that the principal component fraction matrix is calculated by splicing the characteristic vector into an input matrix with a defined shape so that each row of the input matrix is the structural eigenvector of a sample. As such, said steps are directed to judicial exceptions. The instant Specification (see Para. [0040]) also discloses that visualization may be performed to identify the relationship between samples, and this visualization can include embedding the principal components in a visualized cell type atlas. Therefore, the claimed steps are not further defined beyond something that reads on performing a calculation using a computer as a tool, and merely looking at data and making a determination. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). Independent claims 1 and 17 do not recite any additional elements.
Additionally, none of the recited dependent claims recite additional elements which would integrate the judicial exception into a practical application. Specifically, claims 12-13 recite an extra solution activity of data visualization, claim 14 recites instructions to implement an abstract idea on a generic computer, and claims 18-19 recite an extra solution activity of generically administering a gene therapy (equating to instructions to “apply” the recited judicial exceptions in a generic way; see MPEP § 2106.04(d)(2)). As such, claims 1-19 are directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
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). Independent claims 1 and 17 do not contain any additional elements.
Since independent claims 1 and 17 do not contain any additional elements, there are no additional elements to recite an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exceptions into a patent-eligible application of the judicial exception. Therefore, the instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1-19 are not patent eligible.
Response to Arguments under 35 U.S.C. 101
Applicant’s arguments filed 5/10/2026 have been fully considered but they are not persuasive.
1. Applicant argues that under Step 2A, Prong One, the proper inquiry is whether the claims are directed to an ineligible concept, rather than merely applying it in a process. Amended claim 1 is not directed to abstract mathematics itself It is directed to a specific improvement in chromatin structure analysis technology that solves concrete technical problems identified in Paragraphs [0006]-[0008] of the specification. The claimed invention solves these problems through specific technical improvements, not by claiming mathematics in the abstract (Applicant’s Remarks, Pg. 17).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP § 2106.04(II)(A)(1) recites:
“Prong One asks does the claim recite an abstract idea, law of nature, or natural phenomenon? In Prong One examiners evaluate whether the claim recites a judicial exception, i.e. whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims "set forth" an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words "intermediated" or "settlement." … If the claim recites a judicial exception (i.e., an abstract idea enumerated in MPEP § 2106.04(a), a law of nature, or a natural phenomenon), the claim requires further analysis in Prong Two. If the claim does not recite a judicial exception (a law of nature, natural phenomenon, or abstract idea), then the claim cannot be directed to a judicial exception (Step 2A: NO), and thus the claim is eligible at Pathway B without further analysis.”
Following the flow chart for eligibility analysis, Step 2A, Prong One asks whether the claim recites an abstract idea, law of nature, or natural phenomenon. In the instant case, independent claim 1 recites the following abstract ideas, as described in the rejection above: “performing a correlation process…”, “calculating a structural characteristic vector based on the correlation …”, “calculating a principal component fraction matrix from the structural characteristic vector…”, and “identifying at least one chromatin structural characteristic in the principal component fraction matrix…”. Independent claim 17 recites the following abstract ideas, as described in the rejection above: “identifying at least one chromatin locus exhibiting a structural aberration in said chromatin structural characteristic…” and “outputting an identifier of said at least one chromatin locus as a candidate target for cancer intervention”. These limitations recite mathematical concepts or mental processes as described in the rejection above. Examiner applied appropriate analysis under Step 2A, Prong One to identify the recited the judicial exceptions. Subsequent analysis under Step 2A, Prong Two identifies additional elements that can impose meaningful limits on the judicial exceptions in the form of improvements or practical applications. Therefore, independent claims 1 and 17 are directed to abstract ideas.
2. Applicant argues that under Step 2A, Prong Two, iterative correlation processing using multiple iterations achieves progressive noise reduction. Each iteration suppresses random noise and enhances systematic chromatin interaction patterns, thereby solving the problem of high noise in Hi-C data. Figure 5 confirms that after iteration, the distinction between normal and cancer samples changes from ambiguous to prominent. Multi-scale quantile binarization establishes a multi-scale feature extraction framework in which each quantile defines a distance scale. This overcomes the defect that prior methods only analyze at a single scale as described in [0008]. Windowed neighbor-averaging performed on the correlation matrix captures local similarity patterns along the DNA sequence and reflects local chromatin compaction status, with a window size ranging from 1 to 10,000 loci. PCA followed by embedding into a visualized cell type atlas converts abstract dimensionality-reduced results into a practical cell classification tool that directly distinguishes normal cells from cancer cells. These steps form a cohesive technical solution, not generic data manipulation (Applicant’s Remarks, Pg. 17-18).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP § 2106.04(d)(II) recites:
The analysis under Step 2A Prong Two is the same for all claims reciting a judicial exception, whether the exception is an abstract idea, a law of nature, or a natural phenomenon (including products of nature). Examiners evaluate integration into a practical application by: (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception(s); and (2) evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application, using one or more of the considerations introduced in subsection I supra, and discussed in more detail in MPEP §§ 2106.04(d)(1), 2106.04(d)(2), 2106.05(a) through (c) and 2106.05(e) through (h).
The limitations of “performing a correlation process on the Hi-C matrix to calculate a correlation matrix through a plurality of iterations” (emphasis added), “calculating a structural characteristic vector based on the correlation matrix , wherein calculating the structural characteristic vector comprises at least one of: (i) calculating different quantiles of the correlation matrix and converting the correlation matrix into a binary logical matrix based on each quantile threshold to obtain a one-dimensional structural characteristic vector at multiple scales defined by the quantiles; and (ii) for each locus, extracting a sub-matrix from the correlation matrix based on a window size centered at the locus, and averaging the sub-matrix into a one-dimensional vector whose length equals a number of chromatin bins” (emphasis added), and “identifying at least one chromatin structural characteristic in the principal component fraction matrix by embedding the principal components into a visualized cell type atlas to distinguish between different cell types” (emphasis added) have been identified as judicial exceptions in Step 2A, Prong One above. The integration of a judicial exception into a practical application can only be achieved by additional elements, not by a limitation that recites a judicial exception. Thus, the recited limitations are not considered as an improvement in a classification tool for Hi-C matrices that distinguishes normal cells from cancer cells. This argument is thus not persuasive.
3. Applicant argues that under Step 2B, the step of performing a plurality of iterations to remove noise and underline higher order correlation is not taught in any prior art reference including Dekker, Zhang, or Zhou. The step of converting the correlation matrix into a binary logical matrix based on each quantile threshold to obtain multi-scale structural features is unique to the present application. Zhou uses only a single 80th percentile threshold for clustering and imputation. The step of embedding principal components into a visualized cell type atlas to distinguish different cell types is not taught in any prior art. Additionally, the claimed method follows an ordered sequence, where each steps represents a meaningful transformation toward a practical goal, with examples showing the solution works for several cancers (Applicant’s Remarks, Pg. 18-19).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP § 2106.04(d)(II) recites:
Although the courts often evaluate considerations such as the conventionality of an additional element in the eligibility analysis, the search for an inventive concept should not be confused with a novelty or non-obviousness determination. See Mayo, 566 U.S. at 91, 101 USPQ2d at 1973 (rejecting "the Government’s invitation to substitute §§ 102, 103, and 112 inquiries for the better established inquiry under § 101 "). As made clear by the courts, the "‘novelty’ of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claim falls within the § 101 categories of possibly patentable subject matter." Intellectual Ventures I v. Symantec Corp., 838 F.3d 1307, 1315, 120 USPQ2d 1353, 1358 (Fed. Cir. 2016) (quoting Diamond v. Diehr, 450 U.S. at 188–89, 209 USPQ at 9). See also Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151, 120 USPQ2d 1473, 1483 (Fed. Cir. 2016) ("a claim for a new abstract idea is still an abstract idea. The search for a § 101 inventive concept is thus distinct from demonstrating § 102 novelty."). In addition, the search for an inventive concept is different from an obviousness analysis under 35 U.S.C. 103. See, e.g., BASCOM Global Internet v. AT&T Mobility LLC, 827 F.3d 1341, 1350, 119 USPQ2d 1236, 1242 (Fed. Cir. 2016) ("The inventive concept inquiry requires more than recognizing that each claim element, by itself, was known in the art ... [A]n inventive concept can be found in the non-conventional and non-generic arrangement of known, conventional pieces."). Specifically, lack of novelty under 35 U.S.C. 102 or obviousness under 35 U.S.C. 103 of a claimed invention does not necessarily indicate that additional elements are well-understood, routine, conventional elements. Because they are separate and distinct requirements from eligibility, patentability of the claimed invention under 35 U.S.C. 102 and 103 with respect to the prior art is neither required for, nor a guarantee of, patent eligibility under 35 U.S.C. 101. The distinction between eligibility (under 35 U.S.C. 101 ) and patentability over the art (under 35 U.S.C. 102 and/or 103 ) is further discussed in MPEP § 2106.05(d).
Whether or not the claimed elements appear to be free of the prior art is distinct from subject matter eligibility under 35 U.S.C. 101. Additionally, the prior art indicated by Applicant is not used to determine whether the claimed elements are well-understood, routine, and conventional under Step 2B.
Additionally, as described in the rejection and arguments directly above, only additional elements can provide the technical improvements and amount to significantly more than the recited judicial exceptions. Independent claims 1 and 17 do not recite any additional elements, and therefore there are no additional elements to provide significantly more than the judicial exceptions. Therefore, this argument is not persuasive and the rejection under 35 U.S.C. 101 is maintained.
Claim Rejections - 35 USC § 103
The rejection of claims 1-5, 8, and 12-14 under 35 U.S.C. 103 as being unpatentable over Dekker et al. in view of Zhang et al. is withdrawn in view of Applicant’s amendments to the claims filed 5/10/2026, and Applicant’s arguments were found persuasive (Applicant’s Remarks, Pg. 19-21). Specifically, Dekker et al. in view of Zhang et al. does not teach the calculation of the correlation matrix using multiple iterations; the calculation of the structural characteristic vector using quantiles or using window based averaging; or the calculation of the principal component fraction matrix by splicing, normalizing, and performing dimensionality reduction, as recited in amended claim 1.
The rejection of claims 6-7 and 9-11 under 35 U.S.C. 103 as being unpatentable over Dekker et al. in view of Zhang et al. and Zhou et al. is withdrawn in view of Applicant’s amendments to the claims filed 5/10/2026, and Applicant’s arguments were found persuasive (Applicant’s Remarks, Pg. 21-22). Specifically, Zhou et al. also does not teach the calculation of the correlation matrix using multiple iterations; or the calculation of different quantiles of the correlation matrix.
Conclusion
No claims allowed.
It is noted that claim 17 as currently recited is indefinite because it is unclear what steps are required to determine said chromatin structural characteristic, rendering a meaningful search of the art not possible at this moment. Additionally, claims 18-19 are not enabled, also rendering a meaningful search of the art not possible at this moment. Insofar as prior art is not applied to claims 17-19 in the instant rejection, prior art will be re-assessed upon any amendment.
Claims 1-16 appear to be free from the prior art because the prior art does not fairly suggest or teach the calculation of a correlation matrix using a plurality of iterations, or the calculation of different quantiles of the correlation matrix. The closest prior art is Zhou et al. (Robust single-cell Hi-C clustering by convolution- and random-walk-based imputation, Proc. Natl. Acad. Sci. U.S.A. 116(28): 14011-14018 (2019); published 6/24/2019; cited in the IDS dated 12/3/2024). Zhou et al. discloses a single-cell clustering algorithm for Hi-C contact matrices. The method includes determining a structural characteristic vector based on a single quantile, as well as splicing, normalization, and dimensionality reduction using principal component analysis (PCA), and PCA embedding to visualize differences in cell types. However, Zhou et al. does not teach “performing a correlation process on the Hi-C matrix to calculate a correlation matrix through a plurality of iterations”, “calculating different quantiles of the correlation matrix … to obtain a one-dimensional structural characteristic vector at multiple scales defined by the quantiles”, as disclosed in instant claim 1. Claims 2-16 appear to be free from the prior art due to their dependency on claim 1.
Applicant's amendment necessitated the new grounds 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).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/D.P.S./Examiner, Art Unit 1687
/Lori A. Clow/Primary Examiner, Art Unit 1687
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