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/Restrictions
Applicant’s elections without traverse of the invention of Group 1 (methods of methylation analysis in a blastocyst), and the particular elements of: (i) methylation in a candidate gene; (ii) the pathology autism spectrum disorder; and (iii) the gene SHANK2, in the reply filed on 10/06/2025 is acknowledged.
Claims 3-5 (directed to non-elected pathologies and/or non-elected genes), 9 (directed to non-elected global methylation shift analysis), and 10-20 (directed to non-elected methods and products), are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/06/2025.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. US 63/013,090, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The prior filed provisional application does not provide for the particular limitations of “schizophrenia”, “bipolar disorder”, or “opioid signaling pathway” (as recited in claim 1), or the subgeneric requirement related to “neurodevelopmental disorder candidate genes” (as recited in claim 6). Additionally, the claims of the instant application are directed to “one or more” of the relevant genes, where the provisional application is particular to the analysis/detection of methylation in “two or more autism spectrum disorder candidate genes”.
As such the effective filing date of the instantly claimed methods is the filing date of the parent PCT application, PCT/US21/28422, which is 04/21/2021.
Claim Rejections - 35 USC § 112 - Indefiniteness
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, 2, and 6-8 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.
Claims 1 and 2 are unclear over recitation of the limitation “such that epigenetic dysregulation is …correlated with one or more autism spectrum disorder … candidate genes being hypermethylated”, as recite in claim 1 as consonant with the Election. The claims recite a step of “identifying DNA methylation errors in the blastocyst”, but it is unclear what “errors” are required to be detected such that “epigenetic dysregulation is …correlated with one or more autism spectrum disorder … candidate genes being hypermethylated”. It is unclear if the claims intended to require that methylation in some particular gene (e.g.: SHANK2, as consonant with the Election) is detected at an increased level as compared to some particular reference, or if other methylation errors in other genes can be used as surrogate or proxy markers for the required “one or more autism spectrum disorder … candidate genes being hypermethylated”.
Claims 6-8 are unclear over recitation of the limitation “the level of methylation and gene expression … provides the epigenetic status of the blastocyst”. The limitation requires that there are two components used to provide “the epigenetic status of the blastocyst”- the level of: (i) methylation; and (ii) gene expression. But the claims do not recite any step in which any gene expression level or amount is measured or determined, so it is unclear how these elements are obtained in their use in the claimed methods. Additionally, the claims do not set forth any manner in which the two elements are combined (e.g.: some mathematical formula that is compared to some threshold) to arrive at any “epigenetic status” as required by the claim.
Claim Rejections – Improper Markush Group
Claims 1, 2 and 8 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use.
A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use.
Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of alternative useable associated biological/pathological associations of genes in the recitation “one or more autism spectrum disorder, schizophrenia, bipolar disorder, and/or opioid signaling pathway candidate genes” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use. In this regard it is noted that the different biological/pathological classifications may be distinctly dysfunctional biological pathways related to different genes, and those different genes are themselves each unique biological molecules, as detailed below.
The Markush grouping of alternative genes as identified by gene symbols in the limitations recited in claims 2 and 8 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use. Here it is noted that the election provides for the particular gene that is “SHANK2”. The different gene loci recited in the claims are each unique, with different sequences of nucleotides required for their detection and analysis; and they are related to different encoded proteins with distinct biological roles in a cellular environment. Additionally, with regard to any association with the autism spectrum disorder phenotype (relevant to claim 2), or any association with the broadly recited “neurodevelopmental disorder” (as recited in claim 6, from which claim 8 depends), as asserted in the specification, any particular gene locus may have a different strengths of association with the phenotype (e.g.: Tables 7-10 of the specification) indicating that each individual locus, may be associated with any different phenotype with a different level of reliability.
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, and 6-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas (e.g.: mental processes) and a natural phenomenon without significantly more.
Claim 1, from which claim 2 depends, is directed to a method for identifying increased epigenetic dysregulation, and recites a step of identifying methylation errors and correlating epigenetic dysregulation with one or more autism spectrum disorder being hypermethylated. The claims are thus directed to the assessment of collected data, which is and abstract idea that is a mental process (e.g.: MPEP 2106.04(a)(2)(III)(A)); it is the observation and evaluation of information to reach a judgment or conclusion.
Similarly, claim 6 recites a method of determining epigenetic status, and recites that a level of methylation and gene expression in the one or more neurodevelopmental disorder genes provides the epigenetic status of the blastocyst. The claims are thus directed to the assessment of collected data, where the evaluation of methylation and gene expression provides a status.
Additionally, where the claims include aspects of methylation errors being associated with epigenetic dysregulation (claim 1), and methylation and gene expression being associated with epigenetic status (claim 6), such associations are accepted parts of how a biological organism functions (e.g.: methylation/epigenetic associations with gene expression), and as such these elements of the claims are a natural phenomenon (e.g.: MPEP 2106.04(b)(I)).
This judicial exception is not integrated into a practical application because there are no practical steps related to the correlation of epigenetic dysregulation (claim 1) or determined epigenetic status (claim 6). There are no additional steps of the claims that are directed to applying or using the judicial exception(s) noted above (e.g.: MPEP 2106.04(d)(I)). The claims end with an asserted association (the identifying or determining) of methylation with dysregulation (claim 1), or methylation and expression with epigenetic status, each of which is an abstract idea (as noted above).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims only broadly recite steps of identifying methylation errors (claim 1) or levels (claim 6) in a blastocyst. However, such steps were well understood, routine and convention in the prior art (e.g.: MPEP 2106.05(d)). For example, Tignanelli et al (2018) (cited on the IDS of 04/21/2023 as reference C4 (Denomme (2018))) teaches Methyl-MaxiSeq applied to bisulfite converted blastocyst DNA, and the confirmation of methylation in the SHANK2 gene. Additionally in this regard it is noted that Zhu et al (2017) teaches single-cell whole-genome bisulfite sequencing of blastocyst cells, including the analysis of the genomic locus of the SHANK2 gene (e.g.: Supplementary Table 4).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, and 6-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tignanelli et al (2018) (cited on the IDS of 04/21/2023 as reference C4 (Denomme (2018)).
Relevant to claims 1, 2 and 6-8, Tignanelli et al teaches Methyl-MaxiSeq applied to bisulfite converted blastocyst DNA, as well as RNA-seq performed on blastocyst RNA. The reference teaches identifying increased methylation in advanced paternal age (APA) blastocysts as compared to young paternal blastocysts, including increased methylation associated with altered expression of the SHANK2 gene.
Requirement for Information
Applicant and the assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application.
The Examiner has identified the following citation/reference that is relevant to the instantly claimed subject matter:
M. Denomme Tignanelli; B. McCallie; J. Parks; N.I. McCubbin; W.B. Schoolcraft; M. Katz-Jaffe. “Epigenetic dysregulation in blastocysts derived from advanced paternal aged fathers include autism spectrum candidate genes” Fertility and Sterility, ISSN: 0015-0282, Vol: 110, Issue: 4, Page: e109 Publication Year: 2018.
The reference is cited on the IDS of 04/21/2023 as reference C4, Denomme (2018).
The authorship of the cited reference includes inventors of the instant application, and appears to be the abstract associated with an oral presentation (O-264 Wednesday, October 10, 2018 12:00 PM) that was part of the American Society for Reproductive Medicine (ASRM) Scientific Congress and Expo, held October 6-10, 2018, in Denver, Colorado.
The Examiner requires additional information in order to make further determinations about the patentability to the instant claims. In response to this requirement, please provide:
1. Any material (e.g.: slides; poster panels; figures; descriptive paragraphs) that was presented in association with the cited abstract as a part of the oral presentation of the ASRM Scientific Congress and Expo.
The fee and certification requirements of 37 CFR 1.97 are waived for those documents submitted in reply to this requirement. This waiver extends only to those documents within the scope of this requirement under 37 CFR 1.105 that are included in the applicant’s first complete communication responding to this requirement.
Any supplemental replies subsequent to the first communication responding to this requirement and any information disclosures beyond the scope of this requirement under 37 CFR 1.105 are subject to the fee and certification requirements of 37 CFR 1.97.
The applicant is reminded that the reply to this requirement must be made with candor and good faith under 37 CFR 1.58. Where the applicant does not have or cannot readily obtain an item of required information, a statement that the item is unknown or cannot be readily obtained may be accepted as a complete reply to the requirement for that item.
This requirement is an attachment of the enclosed Office action. A complete reply to the enclosed Office action must include a complete reply to this requirement. The time period for reply to this requirement coincides with the time period for reply to the enclosed Office action.
Conclusion
No claim is allowed.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683