DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
Applicant's election with traverse of Group I (claims 1-6) is acknowledged. Applicant argument that Group I and II share the same special technical feature (an integrated algorithm for selecting normalization control peaks for normalization of ATAC-seq data) is not persuasive. In response, Group I requires additional technical features that are not required by Group II (e.g. aligning and peak calling, and selecting overlapped peaks between cell samples among the peaks). Moreover, the special technical feature of “selecting” as peak having a particular coefficient of variation (as required by Group I) is not technically equivalent to “deriving” an ATAC-seq normalization factor through a well-defined formula (as required by Group II). As such, the Groups are still deemed to lack unity of invention for reasons set forth in the restriction mailed 04/15/2026 because they are not so linked as to form a single general inventive concept under PCT Rule 13.1. In addition, Applicant has not submitted any evidence to the contrary. Accordingly, the restriction is maintained. The requirement is still deemed proper and is therefore made FINAL. Claim 7-20 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/15/2026.
Status of Claims
Claims 1-20 are pending.
Claims 1-6 are under examination.
Claim 7-20 are withdrawn.
Priority
Applicant's claim for the benefit of priority under 35 U.S.C. 119(a)-(d) is acknowledged. This application is the National Stage filing under 35 USC 371 of PCT/KR2020/015066, filed on 10/30/2020, which claims priority to earlier filed REPUBLIC OF KOREA application 10-2020-0002829, filed 01/09/2020, and REPUBLIC OF KOREA application 10-2020-0136246, filed 10/20/2020. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
After further consideration, applicant's priority claim is denied. A U.S. non-provisional utility application containing a foreign priority claim, or its earliest parent application under 35 U.S.C. 120, must have been filed within 12 months of the FIRST filed foreign application disclosing the claimed invention. See 37 CFR §1.55, § 1.63(c)(2), § 1.76(b)6, and MPEP § 201.13 II. In this case, the instant application was filed 07/11/2022, which is MORE than one year after the international application PCT/KR2020/015066. Accordingly, the effective filing date for the instant application is 07/11/2022.
Information Disclosure Statement
The information disclosure statement (IDS) document(s) submitted is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
Drawings
The drawings filed 07/11/2022 are acknowledged and acceptable.
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 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and ‘as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355).
Guidance: Step 1. Under the broadest reasonable interpretation, the claimed invention (claims 1 being representative) is directed to a method for performing a process (selecting normalization control ) and therefore falls within one of the four statutory categories.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. In this case, the following steps of claim 1 recite an abstract idea:
a) aligning and peak calling cell-derived ATAC-seq data;
b) selecting overlapped peaks between cell samples among the peaks called in step a);
c) selecting a peak coincident with DNase I hypersensitivity consensus peak among the peaks selected in step b);
d) selecting a peak having a coefficient of variation (CV) of less than 0.3 and peak width of less than 500 bp among the peaks selected in step c).
Mental Processes
Under MPEP §2111, during patent examination, claims must be interpreted in their broadest reasonable manner consistent with the specification. This means that examiners consider the claim language in light of the specification as understood by a person of ordinary skill in the art, ensuring that the claims are not unduly narrowed by implicit limitations not explicitly recited in the claim (37 CFR 1.75(d)(1)).
Under the BRI, the recited act of aligning and peaking calling ATAC-seq data set forth or describe observing and/or analyzing data (which scientists can performing using their brains or a pencil and paper). As such, these steps encompass a mental process of observing data and/or manipulating data. MPEP 2106.04(a)(2), section III.
Under the BRI, the recited acts of selecting various types of peaks sets forth or describe manipulating and/or analyzing data (which scientists can performing using their brains or a pencil and paper). As such, these steps encompass a mental process of observing data and/or manipulating data. MPEP 2106.04(a)(2), section III.
It is important to note that “Claims that recite performing information analysis as well as the collection and manipulation of information related to such analysis, have been determined by our reviewing court to be an abstract concept that is not patent eligible. See SAP, 898 F.3d, 1165, 1167, 1168 (Claims reciting "[a] method for providing statistical analysis" (id. at 1165) were determined to be "directed to an abstract idea" (id. at 1168)); see also Content Extraction & Transmission LLC v. Wells Fargo Bank, Nat'l Ass 'n, 776 F.3d 1343, 1345, 1347 (Fed. Cir. 2014). [Step 2A, Prong 1: YES].
Mathematical Concept
Under the BRI, the recited act of selecting a peak having a coefficient of variation (CV) sets forth or describes a mathematical calculation and/or mathematical relationship (since the artisan would recognize a CV is calculated as the ratio of the standard deviation to the mean). While no specific equation is being claimed, Applicant is reminded that there is no particular word or set of words that indicates a claim recites a mathematical calculation. See MPEP 2106.04(a)(2). Similar to the ineligible claims at issue for In re: Board of Trustees of the Leland Stanford Junior University, 991 F.3d 1245 (Fed. Cir. 2021), the instant claims are written effectively as a method for mathematically manipulating or relating data to ascertain additional data. As such, this step recites a mathematical concept. MPEP 2106.04(a)(2) Section I. [Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. In this case, there are no additionally recited steps or elements appended to the abstract idea. Therefore, by definition, there are also not additional steps/elements that integrate the recited judicial exception into a practical application. [Step 2A, Prong 2: NO].
C. Guidance Step 2B:
Under the 2019 PEG, a conclusion that an additional element is insignificant extra-solution activity in Step 2A should be re-evaluated in Step 2B. In this case, the claims do not include any additional steps and/or elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s). [Step 2B: NO].
Dependent Claims
Dependent claims 2-6 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. Regarding claim(s) 2-6, these are directed to limitations that further limit the specificity of the abstract idea set forth above or the nature of the data being used by the abstract, and therefore are also recite mathematical concepts for reasons discussed above in the Step 2A (prong 1) analysis. Therefore, the claims as a whole are not patent eligible. For additional guidance, applicant is directed generally to the October 2019 Revised Patent Subject Matter Eligibility Guidance.
Claim rejections - 35 USC § 112b
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 1-6 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 pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 1 are also rejected due to said dependency.
Claim 1 recites “A method for selecting normalization control peak for normalization of ATAC-seq” (in the preamble). Firstly, it is unclear as to the metes and bounds of a “normalization control peak”. A review of the specification does not provide any limiting definition that would serve to clarify the scope of this term, i.e. in what way is such a peak characteristically different from any other of the recited peaks. The specification does teach [on page 2] an intended use of such peaks to “correct the amount of the sample for quantitative analysis”. However, this is not commensurate in scope with what is claimed and Applicant is reminded that intended use recitations do no impose any patentable weight. Secondly, the claim results in selecting a peak having a coefficient of variation (which is not equivalent to a normalization control peak based on the plan meaning of the claim). Therefore it is unclear in what way the claim achieves the purpose of the preamble. Applicant is reminded that a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone [See MPEP 2111.02]. Clarification is requested via amendment.
Claim 1 recites “aligning…cell-derived ATAC-seq data”. In this case, it is unclear what limiting effect is intended by “cell-derived ATAC-seq” data, which suggests that a physical assay (ATAC-seq) is being performed on a cell, but does not explicitly require any such limitation. Applicant is reminded that claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular function. See MPEP 2111.04. The specification states “directly performing ATAC-seq using a cell sample” [page 8]. However, this is not commensurate in scope with what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01Clarification is requested via amendment.
Claim 1 recites “c) selecting a peak coincident with DNase I hypersensitivity consensus peak among the peaks selected in step b).” In this case, it is unclear what is meant by a “peak coincident with DNase I hypersensitivity consensus peak.” There is no previous mention of DNase I, any active method step that explicitly requires using DNase I (e.g. performing a DNase-seq assay), or any active method step for obtaining peak data associated with DNase I. Accordingly, there is lack of antecedent basis for a peak coincident with DNase I hypersensitivity. In addition, the claim is relying upon information that has not been previously obtained (peak data associated with DNase I) to select a “coincident peak” and therefore also appears to be missing essential subject matter (e.g. performing an ATAC-seq assay, performing a DNase-seq assay and comparing peak results). Lastly, it is unclear in what way a “coincident” peak is being selected such that the artisan would now how to avoid infringement, i.e. how is an overlapping peak different from a coincident peak. The specification does not provide any limiting definitions, specific properties, or scoring criteria indicating the scope of this term, i.e. the result is subjective and imperceptible. Clarification is requested via amendment.
Claim 1 recites “d) selecting a peak having a coefficient of variation (CV) of less than 0.3 and peak width of less than 500 bp among the peaks selected in step c).” In this case, this limitation suggests that a CV (which is characteristic of the peak) has been previously calculated for a certain peak without explicitly requiring any such limitation. As a result, this step renders the claim indefinite. Applicant is reminded that claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular function. See MPEP 2111.04. As a result, the claim also appears to be missing essential subject matter (e.g. performing one or more CV calculations such that the optimal one can be selected). Clarification is requested via amendment. Clarification is requested via amendment.
Claim 3 recites “wherein the cell is one selected from…”. There is lack of antecedent basis for “the cell” because parent claim 1, as discussed above, does not explicitly recite or use a “cell” and the claim does not explicitly recite performing an ATAC-seq assay (but merely analyzing data). At best, parent claim 1 recites “aligning and peak calling cell-derived ATAC-seq data”. As a result, it is also unclear in what way claim 3 further limits the subject matter of parent claim 1. Clarification is requested via amendment.
Claim 4 recites “A normalization control peak selected by the method of claim 1.” This phrase is a product-by-process type limitation directed to how the data is generated. However, claim 1 does not result in selecting a “normalization control peak”. As such, it is unclear what positive process steps are minimally required to achieve the function of parent claim 4. Clarification is requested by amending the claim to provide a clear-cut indication of the functionality performed by the claimed method using active language. Applicant is also reminded that MPEP Section 1.75(b)(2) provides that a claim that refers to another claim but does not incorporate by reference all the limitations of the claim to which such claim refers will be treated as an independent claim.
Claim 5 recites “The normalization control peak of claim 4 comprising at least one selected from the group consisting of SEQ ID NO: I to SEQ ID NO: 232.” In this case, while a peak can be associated with a particular sequence (e.g. to indicate if a particular gene is present), it is unclear in what way a peak can “comprise” a particular SEQ ID number as claimed. Moreover, while is it noted that ATAC-seq is an assay “using sequencing” (as set forth in claim 1), neither parent claim 4 (nor claim 1) explicitly provides any limitation directed to sequence data (such that is can be limited to a particular SEQ ID). For these reasons, it is unclear in what way claim 5 further limits the subject matter of parent claim 4 (or parent claim 1). Clarification is requested via amendment.
Claim 6 recites “The normalization control peak of claim 5, wherein the normalization control peak includes one or more selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.” This limitation mirrors that of claim 5 is thus is problematic for the exact same reason set forth above. In particular, while a peak can be associated with a particular sequence, it is unclear in what way a peak can “comprise” a particular SEQ ID number. Clarification is requested via amendment.
Cited Prior Art
In light of the claim rejections for indefiniteness under 35 U.S.C. 112(b), as set forth above, the Examiner was not able to perform a meaningful search of the prior art. In the interest of advancing prosecution, the following prior art made of record and not presently relied upon is considered pertinent to applicant' s disclosure. Applicant is reminded that prior art rejections under 35 U.S.C. 102 and/or 35 U.S.C. 103 may be applied in the next Office action in light of applicant's amendments, and that the next Office action can properly be made "Final" if these rejections are necessitated by amendment. See MPEP 706.07.
Corces et al. (Science, 2018, vol. 362, 420, pp.1-13) teaches routine and conventional assays for transposase-accessible chromatin using sequencing (ATAC-seq) that include aligning and peak calling.
Grandi et al. (Nature Protocols, 2022, volume 17, pages 1518–1552; Pub. Date: April 27, 2022) teaches an optimized assay for transposase-accessible chromatin using sequencing (ATAC-seq) that provides a simple and scalable way to detect the unique chromatin landscape associated with a cell type and how it may be altered by perturbation or disease. The describe an updated and optimized protocol for ATAC-seq, called Omni-ATAC, that is applicable across a broad range of cell and tissue types.
Yan et al. (Genome Biology, 2020, 21:22, pp.1-16) teaches that the Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) is widely used in studying chromatin biology and provides a review of the major steps in ATAC-seq data analysis, including pre-analysis (quality check and alignment), core analysis (peak calling), and advanced analysis (peak differential analysis and annotation, motif enrichment, footprinting, and nucleosome position analysis).
Wang et al. (NATURE COMMUNICATIONS, 2018, 9:1364, pp.1-13) teaches a method of ATAC-Seq analysis and reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.
Smith et al. (NAR Genomics and Bioinformatics, 2021, Vol. 3, No. 4, pp.1-9) teaches PEPATAC, a program and ATAC-seq pipeline that is easily applied to ATAC-seq projects of any size, from oneoff experiments to large-scale sequencing projects. In particular, PEPATAC leverages unique features of ATAC-seq data to optimize for speed and accuracy, and it provides several unique analytical approaches. Output includes convenient quality control plots, summary statistics, and a variety of generally useful data formats to set the groundwork for subsequent project specific data analysis.
Pomnaluri et al. (US2019/0211404; Pub. Date: Jul. 11, 2019) teaches methods for analyzing chromatin using DNase-seq (DNase I hypersensitivity site sequencing), FAIRE-seq (Formaldehyde Assisted Isolation of Regulatory Element sequencing; FAIRE) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) [0003]. The teach comparing their method with DNase I hypersensitivity sequencing (DNase-seq) in terms of sensitivity and specificity [0206]. DNase-seq data was downloaded from ENCODE. Sequencing reads were mapped and open chromatin peaks were called using MACS2 with the same parameters as the NE-seq experiment. Overlapped open chromatin peaks in both methods were identified using DiffBind package in R. Distribution of the peaks was visualized using IGV browser (see FIG. 8A-8C).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
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