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 .
This Office Action is in reply to Applicants’ correspondence of 05/11/2026. Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Please Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
In the reply filed on 10/06/2025 Applicants elected without traverse, 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to non-elected global methylation shift analysis), and 10-20 (directed to non-elected methods and products), remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as set forth on page 2 of the Office Action of 01/09/2026.
Withdrawn Claim Rejections - 35 USC § 112 - Indefiniteness
The rejection of 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112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth on pages 3-5 of the Office Action of 01/09/2026, are withdrawn in light of the amendments to the claims.
New Claim Rejections - 35 USC § 112 – Indefiniteness
Necessitated by Claim Amendments
Claim 23 is 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 23 is unclear over recitation of the limitation “the candidate gene of the third blastocyst having the hypermethylated shift is” because there is no antecedent basis for any “candidate gene”, “third blastocyst” or “hypermethylated shift” in either claim 23 or in claim 21 from which claim 23 depends. The rejected claim may be more clear if amended to depend from claim 22.
Maintained Claim Rejections – Improper Markush Group
Newly Applied to Newly Presented Claim
Claim 23 is 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 alternatively useable genes in the recitation “the candidate gene of the third blastocyst having the hypermethylated shift is one of” 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 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 claim 23 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 epigenetic dysregulation (as recited in claim) or with a neurodevelopmental disorder (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.
Response to Remarks
Applicants have traversed the rejection of claims as directed to an improper Markush style group of alternatively useable elements. Applicants’ have argued (p.7-8 of the Remarks of 05/11/2026) that the newly presented claims do not include an improper Markush group. The argument is not persuasive because claim 23 is directed to an alternative grouping of different genes similar to the recitation in previously presented claim 2 which was rejected in the Office Action of 01/09/2026 as directed to an improper Markush group.
Maintained Claim Rejections - 35 USC § 101
Newly Applied to Newly Presented Claims
Claims 21-24 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.
The claims are directed to methods for identifying increased epigenetic dysregulation, and recite steps determining a hypo- or hyper-methylation shift to identify increased epigenetic dysregulation based on comparison to methylation levels. The claims are thus directed to the assessment of collected data, which is an 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.
The claims further recite a step of “rejecting” the blastocyst for an implantation procedure, which in its broadest reasonable interpretation is a judgment about the useability for the blastocyst in a procedure.
Additionally, where the claims include aspects of methylation being associated with epigenetic dysregulation and suitability for an implantation procedure, 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)).
The judicial exceptions are not integrated into a practical application because there are no practical steps related to the identification of epigenetic dysregulation. 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 “rejecting” a blastocyst for use in an implantation procedure, which is an abstract idea (as noted above, in is a decision not to use the blastocysts). Furthermore, the lack of using something is not a practical because it does not require that any particular step or function be performed (i.e.: it is the absence of any step).
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 measuring global methylation (as recited in claim 21) and methylation of a candidate gene (as recited in claim 22). 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).
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 101 as directed non-patent eligible subject matter. Applicants’ arguments (p.8-11 of the Remarks of 05/11/2026) have been fully considered but are not persuasive to withdraw the rejection.
Applicants’ have initially argued that the newly presented claims do not include any abstract idea because they do not contain limitations that can be performed in the human mind. Applicants have argued that measuring a global DNA methylation is not a limitation that the human mind is equipped to perform. This argument is moot, because the aspect of the claims requiring “measuring a global DNA methylation” is not identified in the rejection as an abstract idea (i.e.: it is addressed as an ‘additional element’ that is data gathering by well understood, routine and conventional methods). With regard to ‘determining … a hypomethylated shift;, the examiner maintains that such a determination may be made by observation of a data table or figure, and can be performed in the human mind. Similarly, a step of ‘identifying … increased epigenetic dysregulation’ based on ‘determining … a hypomethylated shift’ is only the mental processing of information to make a conclusion, and can be performed in the human mind.
Applicants next assert that any judicial exception of the claims is integrated into a practical application because, as disclosed in the application as filed, the presence of epigenetic dysregulation can be tied to adverse outcomes during reproduction, and be used as a basis to remove a blastocysts as a possible in vitro fertilization candidate. This argument is not pervasive because the removal of a blastocyst from candidacy for a procedure, or “rejecting, for use in an implantation procedure” as recited in the claims, is not a requirement for some particular practical step into which the analysis and comparison of blastocysts features is integrated. As noted in the rejection, the “rejecting” of a blastocyst, as recited in the claims is properly interpreted as only a decision (which is a mental process) to not use the blastocyst. Furthermore, the recitation in the claims may only require that the blastocyst is not used, but not using something is not a requirement for a practical application in which that item is included.
Withdrawn Claim Rejections - 35 USC § 102
The rejection of claims 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)), as set forth on page 9 of the Office Action of 01/09/2026, is withdrawn in light of the amendments to the claims.
New Claim Rejections - 35 USC § 103
Necessitated by Newly Presented Claims
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.
Claim(s) 21-24 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Tignanelli et al (2018) (cited on the IDS of 04/21/2023 as reference C4 (Denomme (2018); slides of the associated presentation were provided with Applicants reply of 05/29/2026) in view of Brezina et al (2012).
Relevant to claims 21-24, Tignanelli et al teaches Methyl-MaxiSeq (relevant to claim 24) applied to bisulfite converted blastocyst DNA, as well as RNA-seq performed on blastocyst RNA. Relevant to claim 21, the reference teaches identifying a shift to hypo-methylation in advanced paternal age (APA) blastocysts as compared to young paternal blastocysts (slides 3 and 4). Relevant to claim 22, the reference the reference teaches identifying a SHANK2 (relevant to claim 23) hypermethylation in advanced paternal age (APA) blastocysts as compared to young paternal blastocysts (slides 7, 8 and 10). Relevant to the claims as they recite “epigentic dysregulation”, Tignanelli et al teaches that changes in methylation are indicative of a compromised epigenetic landscape.
Tignanelli et al does not explicitly teach rejecting a blastocyst for use in an implantation procedure. However, the use of preimplantation genetic (PG) testing as a basis for making decision about embryo implantation after an in vitro fertilisation (IVF) cycle was known in the prior art and taught by Brezina et al.
Relevant to the methods of the instantly rejected claims, Brezina et al teaches that PG diagnosis can identify genetic content by various methods including DNA sequencing (e.g.: p. 1 - What is PG diagnosis?), and that the information from PG diagnosis can be used to determine which embryos will be optimal for subsequent uterine transfer.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have rejected a blastocyst identified as having a global hypomethyation shift, and to have rejected a blastocyst identified as having a SHANK2 hypermethyation shift, as taught by Tignanelli et al, for use in an implantation procedure. The skilled artisan would have been motivated to reject a blastocyst for use in an implantation procedure based on the expressed teachings of Brezina et al that PG testing comprising genetic testing conducted on oocytes or embryos after an IVF cycle can provide results that allow decisions to be made regarding which embryos are optimal for transfer into the maternal uterus. The skilled artisans would have been motivated to reject blastocysts with global hypomethyation shift and SHANK2 hypermethyation shift based on the expressed teachings of Tignanelli et al that such epigenetic detections are found in blastocysts from advanced paternal aged fathers, and that such epigenetic detections impact future development, resulting in consequences throughout the lifetime of the individual, and be part of a mechanistic link between the advanced paternal age effect and childhood neurodevelopmental disorders. The skilled artisan would thus recognize that rejecting blastocysts with indicators of impacted future development or childhood neurodevelopmental disorders would prevent such disorders.
Requirement for Information
Applicants’ reply of 05/29/2026 has satisfied the Requirement for Information as set forth on pages 9-11 of the Office Action of 01/09/2016.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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