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 .
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 4-8, 10, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sepp et al. (Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant-negative effects, 2012).
Regarding claim 1: Sepp discloses the impact of various deletions and truncating mutations in the transcription factor 4 gene (TCF4) and that all mutations did not inherently result in complete loss-of-function. (Pg 2873, Introduction) Specifically, Sepp discloses the impact of PTHS-associated mutations on the ability of TCF4 to activate transcription by using HEK293 cells transfected with a firefly luciferase vector comprising 12 µE5 boxes in front of a minimal promoter and either wild type or mutant TCF4-B encoding constructs. (pg 2881, Results) This reads on use of a recombinant nucleic acid construct comprising a mini-promoter operably linked to a coding sequence for a TCF4 polypeptide.
Regarding claims 4-7: Sepp discloses use of 12 µE5 E-boxes in front of the minimal promoter. (pg 2881, Results) This reads on the following claims:
Claim 4: use of between 1-15 µE5 binding motifs
Claim 5: use of at least 5 µE5 binding motifs
Claim 6: use of at least 10 µE5 binding motifs
Claim 7: use of 12 µE5 binding motifs
Regarding claim 8: Sepp specifically discloses that the order of the construct is 12 µE5 binding motifs in front of the minimal promoter and the wild type or mutant TCF4-B encoding constructs. (pg 2881, Results) Sepp further teaches that the general structure of the construct is µE5 – minipromoter – TCF4 coding sequence. (Pg 2885, Materials and Methods) This reads on claim 8 regarding use of a number of µE5 binding motifs in the range of 5-15 and the construct having a general structure of µE5 – minipromoter – TCF4 coding sequence.
Regarding claim 10: Sepp discloses use of both wild type and mutant TCF4-B encoding constructs in the claimed invention. (pg 2881, Results)
Regarding claim 30: Sepp discloses use of a reporter assay using HEK293 cells transfected with a firefly luciferase vector carrying 12 µE5 boxes in front of the minimal promoter followed by the wild type or mutant TCF4-B encoding construct. (pg 2881, Results) This reads on use of a recombinant cell comprising the recombinant nucleic acid of claim 1.
Claim Rejections - 35 USC § 103
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 9 is rejected under 35 U.S.C. 103 as being unpatentable over Sepp et al. (Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant-negative effects, 2012) in view of Saetrom et al. (US 2018/0305689 A1)
The teachings of Sepp are disclosed above. Sepp fails to teach use of a sequence which matches the claimed SEQ ID NO. 10.
Regarding claim 9: Saetrom et al. teaches saRNAs which are useful in upregulating the expression of target genes and therapeutic compositions comprising said oligonucleotides. (57) Specifically, Saetrom teaches that the present invention may be used with microRNAs (miRNAs) (0126) and that the present invention provides compositions for modulating target gene expression/function for therapeutic purposes. (0010) In addition to this, Saetrom specifically lists TCF4 as a suggested gene with which the microRNA compositions can be used to modulate. (0100) Saetrom teaches a variety of compositions, including SEQ ID NO. 1975863, which fully matches the claimed SEQ ID NO. 10, as shown in the alignment chart below:
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It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Saetrom of a sequence matching the claimed SEQ ID NO. 10 with the teachings of Sepp of a nucleic acid sequence comprising a general structure of µE5 – minipromoter – TCF4 coding sequence to create a nucleic acid sequence with a sequence matching the claimed SEQ ID NO. 10. One would have had motivation and a reasonable expectation of success at doing so based on the teachings of Saetrom, who detail use of the disclosed sequence in micro RNAs and that the sequences are useful for modulating gene expression/function in a therapeutic setting, along with specifically listing the TCF4 gene as a suggested target for the miRNAs of the claimed invention.
Response to Arguments
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive. From the Examiner’s understanding of the arguments presented, Applicant’s primary argument is that Sepp et al. fails to explicitly disclose that the one or more microE5 motifs are operably linked to a coding sequence for a TCF4 polypeptide. This is unpersuasive, as the commonly accepted definition of the phrase “operably linked” is that of two or more components of a sequence in which the components have a functional relationship with each other per Law Insider. (see PTO-892)
Applicant further argues that Sepp fails to disclose a recombinant nucleic acid construct comprising “a coding sequence for a TCF4 polypeptide” as is recited in claim 1. This is unpersuasive. Sepp very clearly states that multiple variations of the TCF4-B expression construct were created explicitly to identify PTHS-associated missense mutations.; In addition, Sepp states use of WT TCF4-B encoding constructs in HEK 293 cells. (Pg 2876, Results) Furthermore, Sepp states use of a reporter assay using HEK 293 cells transfected with “firefly luciferase luc2P vector carrying 12 uE5 E-boxes in front of the minimal promoter and wt or mutant TCF4-B encoding constructs”. (Pg 2880-2881, Results) This is evidence which shows Sepp makes use of multiple iterations of a TCF4 polypeptide coding sequence. As the phrase “operably linked” has been defined as simply two or more components of a sequence which have a functional relationship with each other as discussed above, it is clear that Sepp does disclose a minimal promoter with 12 microE5 boxes which is operably linked to the TCF4 transcription factor.
Therefore, the 35 U.S.C. 102(a)(1) rejection for claims 1-8, 10, and 30 is upheld.
Applicant lastly argues that, following the discussion of the 35 U.S.C. 102(a)(1) rejection over Sepp et al., the 35 U.S.C. 103 rejection of claim 9 should be withdrawn on the same basis. For the reasons stated above regarding the 35 U.S.C. 102(a)(1) rejection, the 35 U.S.C. 103 rejection regarding claim 9 is upheld.
Conclusion
THIS ACTION IS MADE FINAL. 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 HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/HANNA MARIE THUESON/Examiner, Art Unit 1638
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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