DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claim set received 30 December 2025 has been entered into the application.
Claims 1 and 20 are amended.
Claim 2 is cancelled.
Claims 6-10, 13, and 15-17 are previously cancelled.
Claims 1, 3-5, 11-12, 14, and 18-25 are pending.
Priority
This Application is 371 of PCT/US2019/033845 filed 23 May 2019 which claims benefit to U.S Provisional Applicant 62/793,793 filed 17 January 2019 and U.S Provisional Application 62/675,486 filed 23 May 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 30 December 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
35 USC § 112(b)
It is noted the amendments received 30 December 2025 are necessitated by new ground(s) of rejection.
The rejection of claim 1 under 35 U.S.C § 112(b) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025.
The rejection of claim 3-5, 11-12, 14, and 18-25 under 35 U.S.C § 112(b) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025.
The rejection of claim 2 under 35 U.S.C § 112(b) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025 because the claim was cancelled.
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, 3-5, 11-12, 14, and 18-25 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.
Claim 1 recites “filtering out from the subsequent analysis specific SNP’s…”. The claimed step is rendered indefinite because it is not clear what “subsequent analysis” is referring to. It is not clear if the subsequent analysis is referring to the “identifying step” or another analysis not recited in the claim. It is recommended to amend the claim to recite “filtering out specific SNPs in the subject’s…” and deleting “from subsequently analysis”.
Claims 3-5, 11-12, 14, and 18-25 are rejected because they fail to provide limitations to overcome the deficiencies of the base claim(s).
Claim Rejections - 35 USC § 101
The instant rejection is maintained for reason for record in the Office Action mailed 01 July 2025 and modified in view of the amendments filed 30 December 2025.
The rejection of claim 2 under 35 U.S.C § 101 in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025 because the claim was cancelled.
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, 3-5, 11-12, 14, and 18-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Following the flowchart of the MPEP 2106
Step I - Process, Machine, Manufacture or Composition
Claims 1, 3-5, 11-12, 14, and 18-25 are directed towards a method, so a process.
2A Prong I - Identification of an Abstract Idea
Claim 1 recites
assembling single nucleotide polymorphism (SNP) data from the subject and the subject's biological mother and the subject's biological father
This step can be performed in the human mind by organizing data to assemble single polymorphism (SNP) from a subject’s biological mother and father and is therefore an abstract idea.
comparing the subject's SNP data, the father's SNP data, and the mother's SNP data
This step can be performed in the human mind by observing and comparing subject’s, father’s, and mother’s SNP data and is therefore an abstract idea.
identifying specific SNPs in the subject's SNP data that display non-Mendelian inheritance pattern (NMI)
This step can be performed in the human mind by observing and evaluating the subjects SNP data that displays (NMI) to identify specific SNPs in a subject SNPs and is therefore an abstract idea.
filtering out from subsequent analysis specific SNPs in the subject's SNP data that display NMI and correspond to known structural variation.
This step can be performed in the human mind by observing, comparing, and evaluating information (i.e., nucleic acid data) for filtering data (i.e., SNP’s) and is therefore an abstract idea. This step encompasses performing mathematical comparison (i.e., using equalities and inequalities) for filtering information (i.e., SNP data) which reads on abstract ideas.
identifying at least one de-novo or inherited structural variation in the genome of the subject
This step can be performed in the human mind by observing and evaluating the structural variation in the genome of the subject to determine at least one de novo or inherited structural variation and is therefore an abstract idea.
wherein the structural variation is within or near a gene associated with the subject's disorder or condition
This step describes the location of the structural variation that is analyzed by the abstract idea/mental process.
determining a therapy targeting the gene and treating the subject's disorder or condition
This step can be performed in the human mind by following instructions to determine a therapy and is therefore an abstract idea. This step can be further performed in the human mind by following instructions to treat a subject and is therefore an abstract idea. Here, under broadest reasonable interpretation (BRI), the limitation “treating the subject’s disorder or condition” is broad and reads on abstract ideas.
Claims 5, 12, and 14, and 20-22 are further drawn to further abstract ideas and limitations that describe the abstract ideas of claim 1 and are therefore also abstract ideas.
2A Prong II - Consideration of Practical Application
Claim 1 does not recite any additional element which integrates the recited judicial exception into a practical application because treating the subject’s disorder or condition using the treatments of claims 11 and 18 does not apply or use a particular treatment or prophylaxis for a disease or medical condition. The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). The claim limitation must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. Thus, this treating step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Therefore, the administration step does not integrate the mental analysis step into a practical application. See MPEP 2106.04(d)(2).
Claim 11 does not recite an additional element which integrates the recited judicial exception into a practical application because broadly treating the subject’s disorder or condition does not apply or use a particular treatment or prophylaxis for a disorder or medical condition. The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). The claim limitation must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. Thus, this treating step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Therefore, the administration step does not integrate the mental analysis step into a practical application. See MPEP 2106.04(d)(2).
Claims 18 and 19 do not recite an additional element which integrates the recited judicial exception into a practical application because the particular treatments or prophylaxis (i.e., gene editing of claim 18 and gene editing technology of CRSPR of claim 19) are not utilized for treating for a disorder or medical condition, and the analysis of claim 1 is not specific to ASD and does not utilize and/or correlate any mutations (i.e., NMI SNPs) or specific NMI SNPs to any disease or disorder such that to treat a disease or condition using the treatments of claims 18-19 which only provides a nominal and/or insignificant relationship to the exception. See MPEP 2106.04(d)(2).
Claim 20 does not recite an additional element which integrates the recited judicial exception into a practical application because the abstract ideas are not integrated with the subject’s disorder (i.e., autism) and treating the subject’s disorder (i.e., using the Car T cells). Here, the claim 20 recites administering Car T to treat autism spectrum disorder, but the claims do not utilize and/or correlate any mutations (i.e., NMI SNP’s) or specific NMI SNPs to autism such that Car T cells can be used to treat autism or treat underlying conditions associated with autism. Additionally, claim 1 is not specific to analyzing/determining/identifying autism such that it can be treated with Car T cells (claim 20). Therefore, the combination of autism and particular treatments does not integrate the recited judicial exception because there is no correlation between any NMI SNPs of autism and there is no autism specific analysis (claim 1) such that to integrate said disease or condition (i.e., autism) with administration of a treatment (i.e., Car T cells). Therefore, the administration step does not integrate the mental analysis step into a practical application. See MPEP 2106.04(d)(2).
Claims 23-24 do not recite an additional element which integrates the recited judicial exception of claim 1 into a practical application because reciting generically “treating” the subject’s disorder does not apply or use a particular treatment or prophylaxis (i.e., pharmaceutical or non-pharmaceutical treatment) for a disease or medical condition. See MPEP 2106.04(d)(2).
Claim 25 does not recite an additional element which integrates the recited judicial exception of claim 1 into a practical application because the abstract ideas are not integrated with the subject’s disorder (i.e., autism) and treating the subject’s disorder (i.e., reducing stimuli) and reducing said stimuli. Here, claim 25 recites a non-pharmaceutical treatment (i.e., reducing stimuli) for treating autism spectrum disorder, but the analysis of claim 1 is not specific to autism, and the claims do not utilize and/or correlate any mutations (i.e., NMI SNPs) associated with autism such that to treat autism by reducing stimuli which only provides a nominal and/or insignificant relationship to the exception. Furthermore, “reducing stimuli” is not a particular treatment. For example, it is known “reducing stimuli” can encompass sensory integration therapy, environmental modifications, and behavioral techniques (i.e., sensory diets, noise-canceling headphones, dimmed lighting, weighted blankets, and occupational therapy) to manage sensory overload. Here, the claim does not provide as to what stimuli is being reduced (i.e., light, social settings, noise, cognitive) and/or what method/treatment (i.e., sensory integration therapy, environmental modifications) is reducing the stimuli which provides only a nominal and/or insignificant relationship to the exception. See MPEP 2106.04(d)(2).
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
2B Analysis - Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea.
The recited additional element of data gathering by obtaining SNP of claim 1 does not add more than the recited judicial exception because using SNP data using a chip assay to obtain/gather nucleic acid data is deemed well-known and conventional extra-solution activity. See MPEP See MPEP 2106.05(d)(II) and 2106.05(g).
The recited additional element of using SNP chip array of claims 1 and 3-4 does not add more than the recited judicial exception because using bead chip assays to gather nucleic sequence data that is subsequently analyzed by the abstract ideas is deemed well-known and conventional. See MPEP 2106.05(d)(II). To provide evidence of conventionality, Illumina® teaches using a bead chip that can be customize using upto 400,000 additional markers [page 1 left col overview]. Illumina® teaches the content of the arrays (page 3 table 3 Fingerprint SNPs and Neanderthal SNP) (Cited in the Office Action mailed 26 November 2024)
The recited additional element of using computer processes and equipment of claim 1 does not add more than the recited judicial exception because using computer to store data and abstract ideas is deemed well-known and conventional. See MPEP 2106.05(b).
The recited additional element of using the gene editing technology (claim 18) by using CRISPR (claim 19) does not add more than the recited judicial exception because using gene editing technologies such as CRISPR is deemed well-known and conventional.
The recited additional element of administering CAR T cells as a treatment of claim 20 does not add more than the recited judicial exception because using CAR T cell is deemed well-known and conventional. To provide evidence of conventionality, Greenfield et al. (Greenfield) teach gene editing with respect to bioethics, teach using CRISPR [pages 81-82 box 6.2]. Greenfield teaches using modified T-cell form donors, known as UCART 19 cell, to treat a one-year-old with aggressive lymphoblastic leukemia (ALL) [page 41 box 4.2] (Cited in the Office Action mailed 26 November 2024).
The recited additional element of using pharmaceutical and non-pharmaceutical of claim 23-24 does not add more than the recited judicial exception because treating a subject using pharmaceuticals and non-pharmaceuticals is deemed well-known and conventional.
The recited additional element of reducing stimuli for treating autism spectrum disorder (ASD) of claim 25 does not add more than the recited judicial exception because reducing stimuli is deemed well-known and conventional. To provide evidence of conventionality, Nunez eta l. (Nunez) teach all the experiments were held at the therapy playground, a simple environment with reduced stimuli where children usually attend to train with the therapist [page 839 section III evaluation] (2016 25th IEEE International Symposium on Robot and Human Interactive Communication (RO-MAN), 2016, p.837-842).
In conclusion, and when viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 30 December 2025 have been fully considered but the rejection is maintained.
The Applicant traverses the rejection because 1) when viewed as a whole, the claims are self-evident, 2) cannot be performed in the human mind, and 3) the combination of steps provides significantly more. [remarks, page 7]. The Applicant states the eligibility of the claims is self-evident. The Applicant points to the MPEP 2106.06(a) for guidance. The Applicant states the method of the claims as a whole significantly improves the ability of the genomics field to identify previously discarded candidates that are involved in disease such as autism, multiple sclerosis, and others [remarks, page 7 last para].
In response, with respect to streamline eligibility analysis of MPEP 2106.06(a), claim 1 does not qualify as eligible after Step 2B of the full analysis of the streamlined analysis because the claim lacks self‐evident eligibility. Here, claim 1, as a whole, is merely drawn to gathering and analyzing information (i.e., nucleic acid sequence data) using conventional methods (i.e., computers, clinical/laboratory techniques) for determining a therapy and treating a disorder/condition which is not self-evident because the claim does not integrate the judicial exception such that to provide clear improvement to technology. Here, because the claims do not provide a clear improvement to technology for treating a condition, the claims are not self-evident. Therefore, the argument is not persuasive because as noted in Step 2A Prong II of the 101 analyses above, claim 1 does not integrate the judicial exception and additional elements such to provide a practical application or an improvement to technology as claim 1 is drawn to mere instructions to applying the exception. See MPEP 2106.05(f).
The Applicant states the claim as a whole are directed to an improved technology and technical field. The Applicant state the claims use unconventional processes identifying data that existing technology is either unable to obtain or discards as uninformative. The Applicant points to Enfish and Research Corp. Tech and (‘162) [0024 and 0027] for guidance [remarks, page 8]. It is noted the Applicant refers to U.S Patent Applicant 2021/0210162 (‘162) for guidance [remarks, top of page 10] when referring to disclosure paragraphs [0024 and 0027].
In response and with respect to the claims of Research Corp Tech (RCT) they are drawn to rendering halftone image in a more efficient manner which provided a practical application and improvement to technology whereas the instant claims recite abstract ideas without a practical application as claim 1 recites generic treatment steps for treating a generic disorder/condition. Regarding an improvement of using filtered data, as noted in Step 2A Prong I of the 101 analyses above, the filtering step reads on abstract ideas such as observing, comparing, and evaluating information (i.e., identified SNP’s) for discarding/filtering out data which is insufficient to provide a practical application of the judicial exception. Furthermore, claim 1 identifying at least one de novo step attempts to cover any solution for identifying structural variation (i.e., identifying methods: clinical/laboratory methods, using gene/SNPs related to ASD) with no restriction on how the result is accomplished and with no restriction of the genes/SNP’s used for associating ASD to said patient. Moreover, claim 1 identifying at least one de novo step does not utilize any of the filtered NMI SNPs of previous step such that de novo or inherited structural variation associated with ASD (i.e., indels) can be identified and/or associated with said NMI SNP’s/genes of said subject in order to determine a therapeutic treatment for said subject. Therefore, the claims are drawn to merely applying the judicial exception which is insufficient to provide a practical application or an improvement to technology. See MPEP 2106.05(f).
The Applicant states the claims dramatically improve the functioning of genome analysis by using discarded information. The Applicant states the analysis of nucleic acids is akin to Desjardins. The Applicant states Desjardins “catastrophic forgetting” mirrors the instant claimed process [remarks, page 9]. The Applicant states the instant claimed method mirrors McRO with respect to combined order or rules that renders information into a specific form [remarks, page 9]
In response and with respect to Desjardins, the instant claims do not provide an improvement to technology because the claims are found to be drawn to applying the judicial exception which does not construct a practical application. Moreover, Desjardin provided a solution to the problem of 'catastrophic forgetting' by “learning new tasks in succession whilst protecting knowledge about previous tasks.” Additionally, Desjardins was found to provide an improvement to how the machine learning model itself operates, and not, for example, the identified mathematical calculation. In contrast, the instant claimed method is drawn to instructions for analyzing nucleic acid sequence data for identifying/determining SNPs associated with ASD for subsequent therapeutic intervention.
With respect to McRo, McRo was limited to a specific process for automatically animating characters using rules of different structures and techniques. Here, McRo used these rules in a process specifically designed to achieve an improved technological result in conventional industry practice for lip synchronization animation. By using and incorporating the claimed rules, the method of McRo led to an improvement that allowed computers to produce “accurate and realistic lip synchronization and facial expressions in animated characters” that previously could only be produce by human animators. Therefore, the claims of McRO were found to be a patentable, technological improvement over the existing, manual 3-D animation techniques. The claims of McRo used limited rules in a process specifically designed to achieve an improved technological result in conventional industry practice for lip synchronization animation which was found not to encompass abstract ideas. Whereas, the instant claims are drawn to applying the judicial exception which does not integrate the judicial exception with an additional element(s) to construct a practical application of the abstract idea as noted in Step 2A Prong II of the 101 analyses above.
The Applicant states the claim require a computer to store information and perform analysis that cannot be performed in the human mind. The Applicant points to SRI Int'l, Inc. v. Cisco Systems for guidance. The Applicant states the method cannot be performed in the human mind because the claims utilize a computer to process 1.2 million data points with respect to a child, father, and mother’s genetic structural variation. The Applicant points to para [0068] of US Patent Publication 2021/0210162 (‘162) for guidance. [remarks, top of pages 9-10].
In response and with respect to using computer elements for retrieving/storing electronic data (i.e., nucleic acid sequence data: SNP structural variation) and using computer elements to filter and process structural variation data, the elements are merely tangential to the claimed method. See MPEP 2106.05(b), 2106.05(d)(II), and 2106.05(g). Furthermore, the claimed computer elements are utilized for performing abstract ideas in a computing environment for computing efficiency. See MPEP 2106.05(a)(2)(III)(C). The argument is not persuasive because it is acknowledged that such computations performed mentally, or with paper and pencil, would take considerable time and effort, but that is, of course, the singular purpose of computers and computer networks, to perform large numbers of calculations, via algorithms, rapidly, and without error (assuming no error in user input). Although a general-purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same, and constitutes an abstract idea. See SiRF Tech: "In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations" and Bancorp: "the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter. … Using a computer to accelerate an ineligible mental process does not make that process patent-eligible".
Claim Rejections - 35 USC § 103
The instant rejection is maintained for reason for record in the Office Action mailed 01 July 2025 and modified in view of the amendments filed 30 December 2025. It is noted the amendments received 30 December 2025 necessitated new ground(s) of rejection.
The rejection of claim 1, 3-5, 11, and 21-24 under 35 U.S.C. 103 as being unpatentable over Garg et al. (Cited in the Office Action mailed26 November 2024) in view Illumina® (Cited in the Office Action mailed 26 November 2024) in view of Iossifov et al. ((Cambridge, Mass.), 2012-04, Vol.74 (2), p.285-299) in view of Sahin et al. (Science (American Association for the Advancement of Science), 2015-11, Vol.350 (6263), p.926-926) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025.
The rejection of claim 2 under 35 U.S.C. 103 as being unpatentable over Garg et al. (Cited in the Office Action mailed26 November 2024) in view Illumina® (Cited in the Office Action mailed 26 November 2024) in view of Iossifov et al. ((Cambridge, Mass.), 2012-04, Vol.74 (2), p.285-299) in view of Sahin et al. (Science (American Association for the Advancement of Science), 2015-11, Vol.350 (6263), p.926-926) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025 because the claim was cancelled.
Claim(s) 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Garg in view Illumina® in view of Iossifov in view of Sahin, as applied to claims 1-5, 11, and 21-24, and in further view of Greenfield (Cited in the Office Action mailed 29 May 2024) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025.
The rejection of claim(s) 20 under 35 U.S.C. 103 as being unpatentable over Garg et al. in view Illumina® in view of Iossifov in view of Sahin, as applied to claims 1-5, 11, and 21-24, and in further view of Fransson et al. (Journal of neuroinflammation, 2012-05, Vol.9 (1), p.112-112, Article 576) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025.
The rejection of claim(s) 25 under 35 U.S.C. 103 as being unpatentable over Garg et al. (Cited in the Office Action mailed26 November 2024) in view Illumina® in view of Iossifov in view of Sahin, as applied to claims 1-5, 11, and 21-24, and in further view of Nunez et al. (2016 25th IEEE International Symposium on Robot and Human Interactive Communication (RO-MAN), 2016, p.837-842) in the Office Action mailed 01 July 2025 is withdrawn in view of the amendments received 30 December 2025.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1, 3-5, 11-12, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Belouchi et al. (U.S Patent Pub: US 2009/0081658, Patent Pub Date: 26 March 2009) in view of Iossifov et al. ((Cambridge, Mass.), 2012-04, Vol.74 (2), p.285-299) of view Illumina® (Infinium Exome-24 v1.1 BeadChip (2017)).
Claim 1 recites assembling single polymorphism data from the subject and the subject’s mother and father. Claim 1 recites the SNP data is obtained using a chip assay comprising at least 400,000 SNPs. Claims 1 recites the SNP data is stored as an electronic data on a computer device. Claim 1 recites comparing the SNP data of the subject and subject’s mother and father. Claim 1 recites identifying specific SNPs that display non-Mendelian inheritance patterns. Claim 1 recites filtering out from subsequent analysis specific SNPs in the subject's SNP data that display NMI and correspond to known structural variations removing known structural variations. Claim 1 recites identifying at least one de novo or inherited structural variation in the genome of a subject. Claim 1 recites structural variation within or near a gene associated with the subject’s disease or condition. Claim 1 recites determining a therapy targeting the gene and treating the subject’s disorder.
Belouchi et al. (Belouchi) disclose using a PL-EM algorithm to estimate haplotypes from “genotype” data in 15-marker windows with the results being converted into 15-marker haplotype files. Belouchi discloses individual 15-marker block files are assembled into one continuous block of haplotypes for the entire chromosome. Belouchi discloses the assembling was performed by an assembly algorithm [Belouchi, page 9 left col para 0099]. Belouchi discloses using PPC trios containing parent-parent-child (PPC) trios [Belouchi, page 8 right col, para 0087]. Belouchi discloses preferred samples are those obtained from Crohn disease PPC trios (i.e., mother, father, child) [page 10 left col top para 0106]. Belouchi discloses using 477 family trios [page 25 left col para 0222]. Belouchi discloses using Illumina BeadStations 500GX SNP genotype [page 28 left col para 0247 Example 4]. Belouchi discloses the genotyping information was entered into a Unified Genotype Database (a propriety database under development) [Belouchi page 25 right col para 0224], as in instant claim 1 assembling single polymorphism data from the subject and the subject’s mother and father, the SNP data is obtained using a chip assay, SNP data is stored as an electronic data on a computer device.
Belouchi discloses using PPC trios containing parent-parent-child (PPC) trios [Belouchi, page 8 right col, para 0087]. Belouchi discloses markers were selected from various databases for choosing SNPs and SNP distribution amongst trios was 248,535 SNPs distributed throughout the 383 trios [Belouchi, page 25 right col para 0223]. Belouchi discloses verifying the completeness of the trios datasets and using DataCheck2.1 to calculate statistics per marker and per family [Belouchi, page 25 right col para 0225-0227], as in instant claim 1 comparing the SNP data of the subject and subject’s mother and father. Here, because the trios data sets that are being analyzed contain trios of parents (i.e., mother, father) and child, it is obvious the SNPs from the trios is being compared.
Belouchi discloses using DataCheck2.1 to calculate statistics per marker per family [Belouchi page 25 right col para 0227]. Belouchi discloses analyzing markers (i.e., SNPs of the trios) for observable non-Mendelian segregation [Belouchi, 25 right col para 0232], as in claim 1 identifying specific SNPs that display non-Mendelian inheritance patterns.
Belouchi discloses analyzing markers (i.e., SNPs) for constructing a Genemap for Crohn’s disease [Belouchi, claim 1]. Belouchi discloses SNP’s are markers [Belouchi, page 5 right col para 0064 and page 9 left col para 0091, claim 49]. Belouchi discloses SNP’s and other polymorphisms such as insertions, deletions, microsatellites (i.e., structural variation) [Belouchi, page 1, left col para 003]. Belouchi discloses prior to any analysis, the dataset from GWS was verified for completeness. Belouchi discloses using GGFileMode to remove trios with abnormal family structure or missing individuals and calculated the total number of complete trios per dataset [Belouchi, page 25, right col para’s 0225-0234]. Belouchi discloses using DataCheck2.1 to calculate statistics per marker (i.e., SNP) per family and discloses the acceptance criteria : MAF > 1%, Missing Values < 1%, observed non-Mendelian segregation < 0.33%, and non-significant deviation in allele frequencies from Hardy-Weinberg Equilibrium [Belouchi, pages 25-26, right col para’s 0229-0234]. Belouchi discloses markers that did not meet the criteria were removed. Belouchi discloses using analyses of variance that is performed using the algorithm GenAnova to assess whether families or markers have a greater effect on missing values and/or non-Mendelian segregation. Belouchi discloses the analysis was used to determine the smallest number of data points to remove from the dataset in order to meet the requirements for missing values and non-Mendelian segregation [Belouchi, pages 26, left col para’s 0234], as in claim 1 filtering out from subsequent analysis specific SNPs in the subject's SNP data that display NMI and correspond to known structural variations.
Belouchi discloses a method for treating an individual diagnosed with Crohn’s disease by evaluating the gene expression of at least 200 genes to come up with a treatment plan most effective to the individual [Belouchi page 24 left col para 0215]. Belouchi discloses prognostic assays can be used to determine administered agents to treat Crohn’s disease [page 18 left col, para 0174], as in instant claim 1 determining a therapy targeting the gene and treating the subject’s disorder.
Dependent claim(s): 3-5 and 11-12
Belouchi discloses using Illumina BeadStation 500GX SNP genotype platform [Belouchi page 28 left col para 0247]. Belouchi discloses sequencing methods can be array (i.e., DNA chips) [page 10 right col para 0115], as in instant claim 3.
Belouchi discloses using Illumina BeadStation 500GX SNP genotype platform [Belouchi page 28 left col para 0247], as in instant claim 4.
Belouchi discloses using markers (i.e., SNPs) from SNP database Perlegen Life Sciences, HapMap, dbSNP [Belouchi page 25 right col para 0223]. Belouchi discloses different databases [Belouchi page 28 right col para 0250 table of databases], as in instant claim 5.
Belouchi discloses the present invention further provides other methods of treating Crohn's disease such as administering to an individual having Crohn's disease an effective amount of an agent that regulates the expression, activity or physical state of at least one gene [Belouchi page 24 left col para 0214], as in claim 11.
Belouchi discloses that Crohn’s disease is most frequent in the industrialized world and typical age of onset 15-30 to 60-80 years of age. Belouchi discloses Crohn's disease presently accounts for approximately two thirds of IBD-related physician visits and hospitalizations, and 50 to 80% of Crohn's disease patients eventually require surgical treatment [Belouchi, page 1 left col para 0006], as in claim 12.
Belouchi does not explicitly disclose a chip assay comprising at least 400,000 SNPs, as in claim 1
. Belouchi does not explicitly disclose identifying at least one de novo or inherited structural variation in the genome of a subject, as in claim 1.
Belouchi does not explicitly disclose structural variation within or near a gene associated with the subject’s disease or condition. Belouchi does not disclose claims 21-22
Iossifov teaches observing coincidences between list of genes with disruptive de novo mutations in children with autism and a list of 843 genes products associated with the FRMP genes [page 286 left col top para]. Iossifov teaches analyzing de novo and inherited variants [page 297 left col sequence analysis pipeline]. Iossifov teaches a table of identified SNV’s related to structural variation (i.e., deletion and insertions) corresponding to the FMRP genes [pages 288-289 table 3], as in claim 1 identifying at least one de novo or inherited structural variation in the genome of a subject.
Iossifov teaches the sequence pipeline included 20 bp flanking regions each end of the coding exons [page 286 right col]. Iossifov teaches all reads were mapped within 100bp of the candidate mutation as well as reads that did not map to the assembly but were indicated to have been within 100 bp of the candidate mutation [page 297 right col micro-assembly validation pipeline]. Iossifov teaches a table of SNP located within genes and near genes (UTR) associated with the FMRP target [page 287-289 table 3], as in claim 1 wherein structural variation within or near a gene associated with the subject’s disease or condition.
Dependent claim(s): 21-22
Iossifov teaches de novo gene disruptions in children on the autistic spectrum [title], as in claim 21. Here, because Iossifov teaches de novo gene disruptions in children on the autistic spectrum, Iossifov teaches ASD disorder of claim 21.
Iossifov teaches de novo gene disruptions in children on the autistic spectrum [title], as in claim 22.
Illumina® teaches using a bead chip that can be customize using upto 400,000 additional markers [page 1 left col overview], as in instant claim 1 an SNP chip assay comprising at least 400,000 SNPs. Here, it would be obvious that the bead chip could encompass 400,000 SNP loci.
It would be obvious to one of ordinary skill in the art by the effect filing date of the claimed invention to modify Belouchi in view of Iossifov because Iossifov teaches methods for de novo gene disruptions in children on autism spectrum disorder [title]. One of ordinary skill in the art would recognize that Belouchi and Iossifov are in similar fields of endeavor of analyzing nucleic acids (i.e., gene expression) for determining nucleic acid variation amongst parents and a child. Here, one of ordinary skill in the art would be motivated to combine Belouchi in view of Iossifov because Iossifov teaches methods for analyzing de novo single nucleotide variations (SNV’s) from 343 families comprising parents and at least two siblings [page 286 left col results score and coverage] and using SNP filters for estimating inherited gaps in children with respect to de novo indel rates [page 289 left col de novo indel rates]. As such, there is a reasonable expectation of success combining Belouchi in view of Iossifov because Iossifov teaches unusual coincidence between the list of genes with disruptive de novo mutations in children with autism which analyzes de novo SNVs with respect to a disease or condition (i.e., autism) [page 286 left col]. Here, combining and using the methods of Belouchi in view of Iossifov would yield predictable results that can be utilized for identifying at least one de novo or inherited structural variation in a genome of a subject having or at risk of developing a disorder or condition (i.e., autism/ASD).
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Belouchi in view of Iossifov in view of Illumina® because Illumina® teaches using a bead array chip that can encompass upto 400,000 biomarkers [page 2 table 1]. One of ordinary skill in the art would be motivated to combine Belouchi in view of Iossifov in view of Illumina® because the bead chip array of Illumina® could be used to analyze the SNPs of Belouchi and Iossifov. Here, substituting bead array of Illumina® BeadChip containing at least 400,000 SNP for Bellouchi’s Illumina BeadStation 500GX SNP genotype platform would yield a predictable SNP analysis that can be utilized for identifying SNP variation in a mother’s, father’s, and subject’s genome for determining whether a subject risk of developing a disorder or condition (i.e., Crohn’s or ASD) and for determining a therapy to treat the disorder or condition.
Claim(s) 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Belouchi in view of Iossifov in view Illumina®, as applied to claims 1, 3-5, 11-12, and 21-22, and in further view of Greenfield (Cited in the Office Action mailed 29 May 2024).
Belouchi in view of Iossifov in view Illumina® teach claims 1, 3-5, 11-12, and 21-22.
Belouchi in view of Iossifov in view Illumina® teach a method using bead chips for analyzing SNPs of a subject, a mother, and a father for determining structural variations for treating a disease or condition.
Belouchi in view of Iossifov in view Illumina® does not teach claims 18-19.
Greenfield et al. (Greenfield) teach gene editing techniques and ethical reviews [page 7]. Greenfield teaches using CRISPR-Cas9 technique [page 8], as in claims 18-19.
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Belouchi in view of Iossifov in view Illumina®, and in further view of Greenfield because Greenfield teaches using gene editing tools such as CRISPR. One of ordinary skill in the art would expect a reasonable success in combining Belouchi in view of Iossifov in view Illumina®, and in further view of Greenfield because Greenfield teaches gene editing methodologies across biology that can be applied to animals and humans [page 96 section 7.1]. Here, combining the known gene editing methods of Greenfield with the data analysis methods of Belouchi in view of the ASD structural variations of Iossifov in view of the 400,000 SNP array of Illumina® would yield a predictable method that can be utilized for identifying at least one de novo or inherited structural variation in a genome of a subject having or at risk of developing a disorder or condition and treating the disorders or conditions using gene editing technologies (i.e., CRISPR).
Claim 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Belouchi in view of Iossifov in view Illumina®, as applied to claims 1, 3-5, 11-12, and 21-22, and in further view of Sahin et al. (Science American Association for the Advancement of Science, 2015-11, Vol.350 (6263)).
Belouchi in view of Iossifov in view Illumina® teach claims 1, 3-5, 11-12, and 21-22.
Belouchi in view of Iossifov in view Illumina® teach a method using bead chips for analyzing SNPs of a subject, a mother, and a father for determining structural variations for treating a disease or condition.
Belouchi in view of Iossifov in view Illumina® does not teach claims 23-24
Sahin teaches treating different etiologies of ASD that respond to different therapies such as mTOR inhibitors (TSC and PTEN) [page aab3897-3 fig 3], as in claim 23.
Sahin teaches “pharmacological treatments alone may not be sufficient to reach the optimal outcome without behavioral treatments. Behavioral interventions appear promising in mouse models and could be combined with pharmacological interventions in future clinical trials. While simply correcting the synaptic abnormality with a pharmacological agent may not be sufficient to affect behavioral changes, it could accelerate the rate of learning and sociability in the setting of behavioral interventions.” [page aab3897-6 middle col], as in claim 24.
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Belouchi in view of Iossifov in view Illumina®, and in further view of Sahin because Sahin teaches treating autism and autism spectrum disorders using medications to treat different etiologies of ASD that respond to different therapies such as mTOR inhibitors (TSC and PTEN) [page aab3897-3 fig 3]. As such, combining the SNV analyses of Belouchi in view of ASD structural variations of Iossifov in view at least 400,000 Bead Chip of Illumina®, and in further view of treating ASD of Sahin would construct a predictable data analysis method that would provide SNP data for making a determination to treat ASD using the treatments/therapies of Sahin.
Claim(s) 25 are rejected under 35 U.S.C. 103 as being unpatentable over Belouchi in view of Iossifov in view Illumina® in view of Sahin, as applied to claims 1, 2-5, 11, and 21-24, and in further view of Nunez et al. (2016 25th IEEE International Symposium on Robot and Human Interactive Communication (RO-MAN), 2016, p.837-842).
Belouchi in view of Iossifov in view Illumina® in view of Sahin teach claims 1, 3-5, 11-12, and 21-24.
Belouchi in view of Iossifov in view Illumina® in view of Sahin teach a method using bead chips for analyzing SNPs of a subject, a mother, and a father for determining structural variations for treating a disease or condition.
Belouchi in view of Iossifov in view Illumina® in view of Sahin do not teach claim 25.
Nunez et al. teaches All the experiments were held at the therapy playground, a simple environment with reduced stimuli where children usually attend to train with the therapist [page 839 right col III evaluation], as in claim 25.
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Belouchi in view of Iossifov in view Illumina® in view of Sahin, and in further view of Nunez because Nunez teaches using an environment with reduced stimuli where children usually attend to train with therapist. One of ordinary skill in the art would be motivated to combine to Belouchi in view of Iossifov in view Illumina® in view of Sahin, and in further view of Nunez because Nunez teach using different stimuli (i.e., toys or devices that wiggle in children’s hands [page 838 right col section B]) designed for autistic children. As such, there is a reasonable expectation of success to combine Belouchi in view of Iossifov in view Illumina® in view of Sahin, and in further view of Nunez because Sahin teaches behavioral interventions appear promising in mouse models and could be combined with pharmacological interventions in future clinical trials [page aab3897-6 middle col] and Nunez teaches using turn-taking behavior with paired devices for children with ASD. Here, the combination of Sahin and Nunez would yield a predictable therapy regime using pharmaceuticals and non-pharmaceutical treatments (i.e., reduced stimuli) for treating subjects with ASD.
Response to Arguments
Applicant's arguments received 30 December 2025 have been fully considered and the rejection is withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amendments received 30 December 2025. Here, Belouchi, Iossifov, Illumina, Sahin, Nunez, and Greenfield address the issues raised in the amendments received 30 December 2025.
Conclusion
Claims 1, 3-5, 11-12, 14, and 18-25 are rejected.
No claims are allowed.
Finality
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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/J.C.P./ Examiner, Art Unit 1687
/Anna Skibinsky/
Primary Examiner, AU 1635