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 .
Applicant Response
Applicant's response, filed 06/11/2025, 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 Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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. They constitute the complete set presently being applied to the instant application.
Claim Status
Claim 70 is newly added.
Claims 3, 7-8, 16, 19-35 and 38-69 are canceled.
Claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 are pending and under examination herein.
Claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 are rejected.
Priority
The instant application filed 10/16/2020 claims priority from provisional application 62/915946, filed 10/16/2019. Claims 1, 36 and 70 recites determining the linkage between the candidate gene and the NCV with the first and second method in parallel, which is not supported by the disclosure of the provisional application 62/915946. As such, the effective filing date assigned to each of the claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 is 10/16/2020. Newly recited portions are necessitated by claim amendments.
Drawings
The drawings were accepted in the office action mailed 02/27/2024.
Claim Rejections - 35 USC § 112
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.
Claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 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 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 amendments.
Claim 1, 36 and 70, and all dependents thereon, recites the limitation “determining, by the processor in parallel with determining the linkage between the candidate gene and the NCV by the first method, a linkage between the candidate gene and the NCV by a second method”. The specification provides support for performing both methods (para 0049-0063). However, there is not support within the specification, nor has Applicant provided such support, for performing them in parallel. Therefore, the limitation introduces new matter.
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 1-2, 4-6, 9-15, 17-18, 36-37 and 70 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. Newly recited portions are necessitated by claim amendments.
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claims 1, 36 and 70 recite determining a linkage between a candidate gene and the NCV by a first method comprising steps of: identifying that the NCV is located in a first chromatin-accessible region representing an active enhancer; identifying a candidate gene whose expression is dependent upon the active enhancer; determining that at least a threshold number of chromatin-chromatin interactions represented by HiChIP paired-end-tags exist between a location of the first chromatin-accessible region representing the active enhancer and the location of a second chromatin-accessible region representing a promoter of the candidate gene, thereby indicating that the promoter of the candidate gene and the active enhancer are physically linked through a long range chromatin interaction in an insulated neighborhood; and linking the candidate gene to the NCV; and determining, in parallel with determining the linkage between the candidate gene and the NCV by the first method, a linkage between the candidate gene and the NCV by a second method comprising steps of: determining that the NCV is located within a linkage disequilibrium (LD) block defined by a pairwise LD measure of the pairwise LD data that is greater than a threshold value, wherein the LD block further comprises a regulatory element as indicated by the chromatin accessibility data and an eQTL variant associated with the candidate gene; and linking the candidate gene associated with the eQTL variant to the NCV in the LD block; determining that the linkage between the NCV and the candidate gene is overlapping between the first method and the second method and selecting a therapeutic that modulates expression of the candidate gene by modulating expression of a target protein that binds at a location of the first chromatin- accessible region representing the active enhancer.
Claims 2 and 37 recite wherein identifying that the NCV is located in the first chromatin-accessible region comprises determining that the active enhancer is positioned at the first chromatin- accessible region using the protein-chromatin binding site pairing data.
Claim 4 recites wherein determining that the active enhancer is positioned at the first chromatin-accessible region using the protein-chromatin binding site pairing data comprises identifying that the active enhancer is not a promoter by comparing the chromatin accessibility data to the protein- chromatin binding site pairing data.
Claim 6 recites wherein identifying the candidate gene comprises: determining a location of a promoter of the candidate gene based on a location of the second chromatin-accessible region in the chromatin accessible data; and constructing an enhancer-promoter (E-P) loop comprising the active enhancer and the promoter of the candidate gene.
Claim 14 recites wherein the threshold number of chromatin-chromatin interactions is represented by three, four, five, six, seven, or eight HiChIP paired-end-tags.
Claim 17 recites wherein the method further comprises: using the transcription factor binding motif data, identifying the target protein that binds at the location of the first chromatin-accessible region representing the active enhancer; determining a signaling pathway that the target protein is involved in; and wherein the therapeutic modulates the signaling pathway.
Claim 18 recites wherein using the transcription factor binding motif data comprises identifying transcription factor binding motif data corresponding to sequences located between the first chromatin-accessible region and the second chromatin-accessible region.
These recitations equate to steps of collecting information, analyzing data and making observations, evaluations and judgements that can be carried out in the human mind. Specifically, determining a linkage between a candidate gene and the NCV by a first method comprising steps of identifying that the NCV is located in a first chromatin-accessible region representing an active enhancer, identifying a candidate gene whose expression is dependent upon the active enhancer and/or affected by the genetic variant, determining at least a threshold number of chromatin-chromatin interactions represented by HiChIP paired-end tags exist between the first and second chromatin-accessible regions, linking the candidate gene to the NCV, determining a linkage between the candidate gene and the NCV by a second method comprising steps of determining that the NCV is located within a linkage disequilibrium (LD) block defined by a pairwise LD measure of the pairwise LD data that is greater than a threshold value, wherein the LD block further comprises a regulatory element as indicated by the chromatin accessibility data and an eQTL variant associated with the candidate gene and linking the candidate gene associated with the eQTL variant to the NCV in the LD block, determining that the linkage between the NCV and the candidate gene is overlapping between the first method and the second method selecting a therapeutic, determining the active enhancer is positioned in the first chromatin-accessible region, identifying the active enhancer is not a promoter by comparing the chromatin accessibility data to the protein-chromatin binding site pairing data and checking for the presence and absence of peaks, determining the location of the a promotor of the candidate gene, constructing an E-P loop, selecting the genetic variant, using the transcription factor binding motif data to identify a target protein that binds at the location of the first chromatin-accessible region, determining a signaling pathway the target protein is involved in, and identifying transcription factor binding motif data corresponding to the sequences located between the first and second chromatin-accessible regions can be practically performing the human mind as claimed and are similar to the concepts of collecting and comparing known information in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011) and collecting information, analyzing it, and reporting certain results of the collection and analysis in Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016) that the courts have identified as concepts that can be practically performed in the human mind. Determining if a limitation recites a mental process does not evaluate if the steps can be performed solely in one mind, but rather if it recites steps that can be performed by human minds, with or without the use of tools, such as a computer. See MPEP 2106.04(a)(2)(III). With respect to the instant steps, two people can determine mentally, in parallel, the linkage between the candidate gene and the NCV by the first and second method. Furthermore, as discussed in the MPEP, the courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. The claims are still considered to recite a mental process even if the claims use a computer as a tool to perform the concept. Therefore, each of the above recited limitations fall under the “Mental Processes” grouping of abstract ideas. Furthermore, the steps as claimed for determining that the NCV is located within a linkage disequilibrium (LD) block defined by a pairwise LD measure of the pairwise LD data that is greater than a threshold value equate to organizing information and manipulating information through mathematical correlations and reciting a mathematical equation, similar to the concepts of taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form in Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). Therefore, these limitations also fall under the “Mathematical Concepts” grouping of abstract ideas. Claims 2, 6, 14 and 18 further qualify the judicial exception. Product claims using a non-transitory computer-readable medium may still recite a mental process. With respect to claims 36 and 37, the steps recited within it are still mental processes, as described above, equate to an abstract idea because it could be "performed by humans without a computer," as decided by the courts in Mortgage Grader 811 F.3d. at 1318, 1324-25, 117 USPQ2d at 1695, 1699-1700. As such, claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to insignificant extra-solution activity:
Claims 1, 36, and 70 recite obtaining a dataset comprising: sequencing or genotyping data comprising a non-coding variant (NCV); chromatin accessibility data identifying chromatin-accessible regions across the genome; and chromatin contact profile describing chromatin-chromatin interactions and chromatin domains; pairwise linkage disequilibrium data measurements for a plurality of alleles; and an expression quantified trait loci (eQTL) dataset comprising a plurality of eQTL variants associated with genes; a processor; a processor in parallel.
Claims 2 and 37 recite wherein the obtained dataset further comprises protein-chromatin binding site pairing data.
Claim 5 recites wherein the chromatin accessibility data corresponding to the active enhancer comprises a peak indicating presence of an active enhancer, and wherein the protein-chromatin binding site pairing data corresponding to the active enhancer lacks a peak, thereby indicating that the active enhancer is not a promoter.
Claim 9 recites wherein the protein- chromatin binding site pairing data comprises CHiP-seq data.
Claim 10 recites wherein the sequencing or genotyping data comprising the NCVs is Genome- Wide Association Study (GWAS) data.
Claim 11 recites wherein the sequencing or genotyping data comprising the NCVs is obtained from whole genome sequencing, whole exome sequencing, targeted of a gene region or panel of genes, or targeted genotyping.
Claim 12 recites wherein the chromatin accessible data is Assay for Transposase-Accessible Chromatin (ATAC) sequencing data comprising ATAC peaks that identify the chromatin-accessible regions across the genome.
Claim 13 recites wherein the chromatin contact profile is HiChIP-seq data comprising HiChIP paired-end-tags (PETs) describing the chromatin-chromatin interactions.
Claim 15 recites wherein at least one of the chromatin-chromatin interactions of the chromatin contact profile is an enhancer- promoter interaction.
Claim 16 recites wherein at least one of the chromatin domains of the chromatin contact profile is an insulated neighborhood.
Claim 17 recites wherein the dataset further comprises transcription factor binding motif data.
Claim 36 recites a non-transitory computer readable medium.
Claims 1, 36 and 70 recite limitations on how data is gathered. Claims 2, 5, 9-13, 15-17 and 37 recite further limitations of the types of data used. These limitations equate to mere data gathering to perform the mental evaluations and judgements, which equate to insignificant extra-solution activity (see MPEP 2106.05(g)). There is no indication that any of these additional elements provide a practical application of the recited judicial exception outside of the judicial exception itself.
Claims 1, 36 and 70 also merely recites using a generic computing systems and computer program products to carry out instructions to implement an abstract idea on a computer. The computer system and computer program product as claimed fails to recite details of how a solution to a problem is accomplished and only recites the idea of a solution or outcome. There are no limitations that indicate that the claimed steps require anything other than generic computing systems, as generic computers are capable of parallel processing. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. Furthermore, the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit).As such, claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). Further analyzing the additional elements under step 2B, the additional elements as described above do not rise to the level of significantly more than the judicial exception. As directed in the Berkheimer memorandum of 19 April 2018 and set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Under broadest reasonable interpretation, the step of obtaining a dataset comprising the recited data encompasses receiving the dataset by a conventional computer (and the dependents further limit the data being received), and the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit).
Therefore, 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, and the claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 are not patent eligible.
Response to applicant’s arguments
Applicant states the instant claims have been amended to recite steps that cannot be performed in the human mind, such as steps performed by a processor and determining the linkage between the candidate gene and the NCV by the first and second method in parallel, as a computer processor is capable of parallel processing the first and second method, but the human mind is not, and therefore, this step is an additional element that provides an improvement in technology or technical field through the improved methodology and integrates the judicial exceptions into practical application (Applicant’s Arguments, p 10, para 2; p 11, para 1-p 12, para 3).
It is respectfully submitted that this is not persuasive. As discussed above, the human mind is capable of performing the steps of both methods. Determining if a limitation recites a mental process does not evaluate if the steps can be performed solely in one mind, but rather if it recites steps that can be performed by human minds, with or without the use of tools, such as a computer. See MPEP 2106.04(a)(2)(III). With respect to the instant steps, two people can determine mentally, in parallel, the linkage between the candidate gene and the NCV by the first and second method. Furthermore, as discussed in the MPEP, the courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. The claims are still considered to recite a mental process even if the claims use a computer as a tool to perform the concept. Therefore, the step for determining using the first and second method in parallel is a mental process, and the claims recite mental processes.
With respect to Step 2A, prong 2, the improvement appears to be solely provided by performing the first and second method, which were found to be judicial exceptions, and the parallel processing by a processor of the two methods does appear to provide the improvement or result in an improvement to technology. As discussed in MPEP 2106.05(a), the judicial exception alone cannot provide the improvement and the improvement cannot be to the judicial exception itself. The additional elements equate to mere data gathering to perform the mental evaluations and judgements, which equate to insignificant extra-solution activity, and mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible. As such, the recited judicial exceptions are not integrated into practical application, and the claims are directed to an abstract idea.
Applicant also states the additional elements amount to significantly more than the alleged judicial exceptions, as the additional elements, of the first method, the second method and performing them in parallel, in combination were not known in the art, and are unconventional or non-routine as evidenced by the lack of prior art rejections in the last office action, and therefore the claims should be found patent eligible and the rejection should be withdrawn (Applicant Arguments, p 12, para 4-p 13, para 4).
It is respectfully submitted that this is not persuasive. As discussed on MPEP2106.05, 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. 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.
Furthermore, as discussed in MPEP 2106.05, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and an inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself. Therefore, only the additional elements of the claims are evaluated both individual and in combination to determine whether they amount to an inventive concept under step 2B. As discussed above, the performing the steps of first and second method in parallel, and determining that the linkage between the NCV and the candidate gene is overlapping between the first and second method are judicial exceptions and are not evaluated under Step 2B, as the use of computer as a tool to perform a mental process is still considered to recite an abstract idea. With respect to the additional elements, as discussed above, the limitations for obtaining data and using a generic computer, which are capable of parallel processing, are well-known, routine and conventional in the art, and therefore do not provide an inventive concept.
Therefore, the claims are not patent eligible and the rejection is maintained.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, 4-6, 9-15, 17-18 and 36-37 under 35 U.S.C. 103 as being unpatentable over Javierre et al. (Cell 2016, 167(5), 1369-1384; previously cited; hereafter referred to as Javierre) as evidenced by Ji et al. (Cell stem cell 2016, 18(2), 262–275; previously cited; hereafter referred to as Ji), and in further view of Mumbach et al. (Nature methods 2016, 13(11), 919–922; previously cited; hereafter referred to as Mumbach) and Zhu et al. (Experimental Biology and Medicine 2017, 242(13), 1325-1334; previously cited; hereafter referred to as Zhu) were withdrawn in the office action mailed 12/11/2024 in view of the claim amendments filed 08/27/2024, as none of Javierre, Mumbach or Zhu appear to disclose determining a linkage between the candidate gene and the NCV by the steps of both the first and second method and determining the linkage between the candidate gene and the NCV is overlapping between the first method and the second method.
Conclusion
No claims are allowed.
Claims 1-2, 4-6, 9-15, 17-18, 36-37 and 70 appear to be free from prior art the closest prior art o Javierre et al. (Cell 2016, 167(5), 1369-1384; previously cited) as evidenced by Ji et al. (Cell stem cell 2016, 18(2), 262–275; previously cited), Mumbach et al. (Nature methods 2016, 13(11), 919–922; previously cited) and Zhu et al. (Experimental Biology and Medicine 2017, 242(13), 1325-1334;previously cited) do not appear to disclose determining a linkage between the candidate gene and the NCV by the steps of both the first and second method and determining the linkage between the candidate gene and the NCV is overlapping between the first method and the second method.
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).
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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/N.D./ Examiner, Art Unit 1686
/Karlheinz R. Skowronek/ Supervisory Patent Examiner, Art Unit 1687