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 .
Application Status
The Amendments and Remarks filed 02 September 2026 in response to the Office Action 05 March 2026 are acknowledged and have been entered. Claim 1 is amended. Claims 2, 6-42 and 45 are canceled. Claims 47-78 are newly added. Claims 1, 3-5, 43, 44, and 46-48 are currently under examination on the merits.
Any objection and rejection not reiterated has been overcome by applicant’s amendments.
Priority
The instant application is a continuation of 371 PCT US22/17371 filed 02/22/2022 which claims priority to application 63/151,222.
Claim Rejections - 35 USC § 112
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.
Claim 1, 3-5, 43, 44, and 46 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 1 recites “an isolated single- or double-stranded synthetic nucleic acid that … hybridizes with, GGCACATGTTCAACTTCTG…” without establishing the extent of pairing or the conditions under which hybridization determines membership in the claimed class. It is unclear whether this alternative requires hybridization across the complete 19-nucleotide sequence under conditions relevant to the recited biological activity or includes partial pairing observable under other conditions.
Claim 1 defines “high identity” as greater than 75% homology, but does not identify whether the percentage is calculated over the complete complementary synthetic sequence or only a locally aligned portion. This distinction matters because the nucleic acid may contain sequence in addition to the recited 19-mer. For example, a 50-nucleotide sequence having a perfectly matching 19-nucleotide segment and mismatches throughout the remaining 31 positions yields 100% identity over the matching segment but only 38% identity over the complete 50-nucleotide sequence. The specification gives nonexclusive BLAST/BLAT examples, different hit-selection criteria, and acknowledges changes in rankings, but does not clearly identify which alignment span controls the claimed threshold [00328, 00337–00342]. Claim 4 additionally permits an unspecified other in silico alignment algorithm. The dependent claims do not resolve the calculation boundary; claims 47–48 narrow the antisense sequence but retain the separate regulatory-region alignment requirement.
Claim 43 requires that the transposon remnant sequence be “not otherwise functional as a transcription factor binding site, primer binding site, small RNA, miRNA, piRNA, siRNA, or eRNA of previously defined function or coding sequence.” The scope of this exclusion is unclear. Specifically, the wording does not clearly establish whether “of previously defined function” qualifies only “eRNA,” the listed RNA categories, or the entire preceding list. Further, “not otherwise functional as” describes an absence of function, whereas the specification describes sequences that have not otherwise been classified as certain functional RNAs. [0004 and 00307]. Consequently, it is unclear whether a remnant possessing one of the listed functions, but not previously identified or classified as possessing that function, satisfies the limitation. Such a remnant would be included under an exclusion based on previously recognized classification but excluded under an exclusion based on actual function. Applicant should clarify the scope of the negative limitation and the categories modified by “of previously defined function.”
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-5, 43, 44, and 46-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, a0s failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 requires a synthetic nucleic acid comprising or hybridizing with GGCACATGTTCAACTTCTG (SEQ ID NO:4077) and comprising a complementary sequence that both targets the transposon remnant specified in limitation (a) and aligns with greater than 75% homology to a regulatory region of another gene specified in limitation (b). The claim further requires the complementary synthetic sequence according to both limitations to augment, alter, or block transcription and/or translation of the other gene, thereby providing the recited gene-to-gene transcriptional signaling and coordinated epigenetic communication.
The specification provides structural and functional disclosures that have been considered. Figure 32Y discloses SEQ ID NO:1553 containing the recited 19-nucleotide sequence, and paragraph [00213] identifies the corresponding sequence group as transposable-element templates for lncRNA LOC105377621. The specification describes synthetic nucleic acids selected to modulate gene-to-gene transcriptional signaling, computational alignment to regulatory regions, and use of identified sequences for pathway modulation. In particular, paragraph [00387] encompasses SEQ ID NO:1553 within the sequences identified for such use [00213, 00253, 00282–00287, 00387–00389; Figure 32Y]. The specification also reports siRNA targeting of the 3′ MLT1J region of RP11-499E18.1 and resulting changes in cell morphology and expression of differentiation markers. [00370–00372; Figures 19–22; Table 9.] Those passages identify the targeted region but do not identify the complementary sequence of the tested reagent. Consequently, they do not connect an identified synthetic complementary sequence comprising or hybridizing with SEQ ID NO:4077 to both its alignment with another gene’s regulatory region and its activity upon that same other gene. Likewise, the MLT1J-associated alignment to GPC5 and the reported changes in differentiation-marker expression are separate disclosures; the cited passages do not identify a complementary sequence for which the claimed alignment and activity upon the aligned gene are disclosed together [00369, Table 8; 00371–00372, Table 9; Figure 32Y]. The broader statements concerning pathway modulation identify the proposed application of the template sequences, while the explanation that shared remnant sequences guide epigenetic chromatin-modifying complexes between functionally linked genes is presented as a hypothesis [00245, 00247–00253, 00374]. Considered together, the cited disclosures describe template sequences, candidate sequence relationships, and regional knockdown results, but do not sufficiently identify the claimed synthetic composition in which the same complementary sequence possesses the recited targeting and alignment relationships and the required activity upon the aligned gene. This conclusion does not require an actual working example for every claimed composition or proof of a complete molecular mechanism. Rather, the disclosure lacks the specific connection needed to convey possession of the claimed combination, either expressly or through identifying characteristics from which that combination would be recognized.
Claim 1 has not been interpreted as requiring the isolated 19-nucleotide sequence alone to perform every recited function. The claim permits additional sequence. Nevertheless, the disclosures identified above do not specify a larger synthetic nucleic-acid embodiment containing or hybridizing with the recited sequence for which the complementary segment, aligned regulatory region, and activity upon the aligned gene are sufficiently connected.
Claims 3 and 4 further limit the alignment relationship or its computational assessment without supplying the missing sequence–activity connection. Claim 5 adds alternative localization signals, identifiers, or modifiers; claim 43 further restricts the targeted remnant; claim 44 specifies an RNA-based nucleic acid; and claim 46 specifies delivery alternatives. Those limitations do not resolve the identified deficiency. Claims 47 and 48 specify antisense sequences to SEQ ID NOs:4077 and 1553, respectively. Their additional structural limitations, including the express disclosure of SEQ ID NO:1553, have been considered. However, the cited disclosure does not connect those particular antisense embodiments to the regulatory-region alignment and activity upon the aligned gene required by incorporated claim 1.
Claim 43 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 43 requires the targeted transposon remnant sequence to be “not otherwise functional as a ….primer binding site.” The application as originally filed does not describe this exclusion expressly, implicitly, or inherently. Paragraphs [0005] and [00309] concerns sequences not previously classified as specified functional RNA types, while paragraph [00258] distinguishes the proposed mechanism from shared transcription-factor binding sites. These disclosures do not address primer-binding-site function. Accordingly, the original disclosure does not provide adequate written-description support for the “primer binding site” negative limitation.
Claims 1, 3–5, 43, 44, and 46 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the disclosed MLT1J-directed knockdown implementation and reasonably predictable variations thereof, does not reasonably provide enablement for the full scope of the claimed functional nucleic-acid genus without undue experimentation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Nature of Invention and Breadth of Claims:
Claim 1 encompasses single- and double-stranded synthetic nucleic acids that comprise the stated sequence or hybridize with it, provided that a complementary sequence additionally meets the remnant-targeting, regulatory-region-alignment, and coordinated gene-signaling requirements. The relevant breadth is this conjunction of structural and functional alternatives, rather than every transposon sequence in the genome or every possible therapeutic application.
Guidance from the Specification
The specification supplies important guidance and working evidence. It identifies the MLT1J template and describes alignment procedures for selecting candidate relationships. It also reports knockdown-associated changes in pancreatic adenocarcinoma cell morphology and expression markers. [00328, 00337–00342, 00370–00373; Table 9; Figures 19–22, 32Y]. These disclosures support the exemplified knockdown route and weigh against treating the application as wholly nonenabling. The unresolved problem concerns extension from that implementation to the broader claimed functional class. A sequence-alignment result identifies sequence correspondence; it does not itself identify which alternative nucleic-acid architectures and target interactions will produce the claimed coordinated regulatory activity. The cited passages do not provide a demonstrated rule connecting the breadth of the hybridizing/comprising alternatives to retention of that activity. They also do not establish that merely meeting the regulatory-region similarity threshold supplies such a rule. The examples therefore provide a starting implementation, but not necessarily a generally applicable means of reaching the claimed functional class.
Experimentation Required/State of the Art
Ordinary skill in synthesis, transfection, alignment, and expression assays reduces the experimental burden. Nevertheless, under the construction stated above, the remaining work would involve selecting additional architectures, determining effective engagement of the relevant remnant, and testing whether each candidate produces the required coordinated regulatory result, rather than only confirming duplex formation or target knockdown. Holdt (Holdt et al. PLoS genetics 9.7 (2013): e1003588) provides a pertinent example of motif changes altering network-associated effects in another lncRNA system. [p. 5, right column, first paragraph under the Alu-motif heading; Figure 5.] That evidence supports caution in extrapolation, but is not proof that every present variant fails. Therefore, practicing the full claimed genus would consequently require repeated candidate identification, TE annotation, SNP/provenance analysis, alignment against other genomic regulatory regions, pathway assignment, synthesis of corresponding nucleic acids, delivery into appropriate cells, and empirical testing of transcriptional/translation effects and network-level signaling. Because the disclosure does not identify a structural rule reliably predicting which members will produce the recited functional result, this work constitutes substantial screening to discover operative members rather than merely routine optimization of known operative embodiments.
Considering the breadth of the claims, the complexity and predictability of the art, the amount of guidance, the limited number of experimentally demonstrated species relative to the genus, and the quantity and nature of experimentation required, the specification does not enable the full presently claimed scope without undue experimentation. The disclosure appears to enable at least the specifically disclosed MLT1J/RP11-499E18.1 embodiment and appropriately defined closely corresponding constructs. The deficiency arises from the additional functional genus encompassed by the present claim language.
Claims 3 and 4 further address regulatory alignment and its computational assessment, but do not themselves supply the missing connection to activity. Claim 5 adds alternative identifiers, localization signals, or modifiers without confining the composition to a demonstrated active architecture. Claim 43 excludes listed target functions; claim 44 specifies an RNA-based nucleic acid; and claim 46 specifies delivery alternatives. Claims 47–48 recite particular antisense sequences to disclosed targets, materially narrowing the variable sequence space. Claims 3–5, 43–44 and 46–48 do not presently cure this scope deficiency for the same reason discussed above: none expressly requires its particular sequence limitation to be the same sequence that performs all functions recited in claim 1. These restrictions also do resolve the identified extension from the demonstrated knockdown route to the asserted broader functional class. If claim 1 were amended to expressly link the SEQ ID NO: 4077/1553-derived sequence to limitations (a) and (b), both the written-description and enablement analyses should be reconsidered on the materially narrower scope.
Response to Arguments
Applicant's arguments, see pgs. 8-10 filed 09/03/2026, with respect to the rejection of claims 1-3, 5-6, 43-44 and 46 under 35 U.S.C. § 103 have been fully considered and are withdrawn. The previously applied references and articulated rationale do not adequately establish that the presently claimed composition, including its recited sequence limitation and the associated targeting, regulatory-region alignment, and functional limitations, would have been obvious. No replacement rejection under 35 U.S.C 103 is made in the action in view of the clarity and support rejections made under 35 U.S.C. 112, as applicable.
The references identified below are considered pertinent to applicant’s disclosure but are not applied in an art rejection. Qu (Qu et al. Mediators of inflammation 2018.1 (2018): 7501851) describes inhibition of RP11-499E18.1 using synthetic siRNA and resulting changes in CXCL16 expression. [Sections 2.8 and 3.7; Fig. 6.] Holdt describes repeat-associated epigenetic trans-regulation involving ANRIL and target-gene promoters. [Figs. 4–5.] These teachings do not, on the present record, establish all limitations of the presently claimed composition in combination.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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