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 12 January 2026 in response to the Office Action 11 August 2025 are acknowledged and have been entered. Claims 1, 3-6, 43 and 44 are amended. Claims 2, 7-42 and 45 are canceled. Claim 46 is newly added. Claims 1, 3-6 43-44 and 46 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 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, 3-6 and 43-44 are 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).”
Claim 1 is directed to a “ composition comprising an isolated single- or double-stranded synthetic nucleic acid and a delivery molecule comprising a complementary sequence that: (a) targets a transposon remnant sequence that is no longer capable of transposition, embedded in a gene within a functional gene pathway and/or a gene network, wherein the transposon remnant sequence being targeted contains single nucleotide polymorphisms (snp) that were dispersed during transposition…”. The terms “transposon remnant sequence” and “single nucleotide polymorphisms” broadly encompasses all polymorphisms that are a part of a transposon remnant sequence. Possession of these claims requires the possession of the genus of every complementary sequence that can bind every transposon remnant sequence that comprises all possible single nucleotide polymorphisms.
The current specification, as filed, discloses that nucleotide substitution errors can occur during the transcription of Transposable elements (TE); and that adjacent DNA or RNA sequences can be incorporated into Transposable elements, resulting in the majority of TEs harboring sequence polymorphisms; thereby generating unique transposable element sequences [0003, 0022; Fig. 1, 2]. The specification further teaches that a TE remnant (TEr) refers to TE no longer capable of transposition [00236].
Regarding transposable elements (TEs) that comprise single nucleotide polymorphisms that renders unique a set of genes sharing gene loci with the snp-containing sequence being targeted, Boris (Boris Umylny et al. Journal of Cellular Biochemistry 102:110–121 (2007)) teach that the short interspersed repeat elements (SINEs), a class of Alu and B1 (i.e., a type TE; non-autonomous retrotransposons that are short, non-coding sequences), which are derived from the 7SL RNA gene, are found all over the human and mouse genome, respectively [abstract]. Boris teach that over 98% of 923,277 Alus and 365,377 B1s examined were unique when queried at full length [abstract]. Boris teach that even at 50% of their lengths, greater than 97% of Alus and 73% of B1s were identified as single-copy sequences [pg. 117, col. 1, para 2]. Therefore, the prior art teaches that there could be over 800,000 unique sequence for just one TE and that these unique sequences need to be screened to be determined. Boris teach searching the entire human and mouse genome for Alus and B1s using BLAST [pg. 113, col. 2, para 3 – pg. 114, col.1, para 2]. Although applicants teaches that it is possible to screen for such gene transcriptional networks, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171).”
The specification does not demonstrate or provide any working examples of a synthetic nucleic acid that targets a transposon remnant sequence that comprises single nucleotide polymorphisms rendering unique a set of genes sharing the sequence targeted. Furthermore, the specification does not demonstrate or provide predictability for generating every synthetic nucleic acid that targets every transposon remnant sequence that comprises all single nucleotide polymorphisms thereby not demonstrating or providing predictability for representatives of the genus. Therefore, considering the extremely large variation in the genus, the failure of the specification to describe or provide predictability of every synthetic nucleic acid that targets every transposon remnant sequence that comprises all single nucleotide polymorphisms or other mutations, and the information provided by the art for the full scope of the claimed genus, it is reasonable to conclude that Applicant did not possess the invention as claimed at the time of filing.
Claims 3-6, 43-44 and 46 do not further limit the genus of nucleic acids so as to resolve the issues above, and are therefore not sufficiently described for at least the reasons above.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3, 5-6, 43-44, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Hannon (US 2009/0062228 A1) in view of Hirose (Hirose et. al. EMBO Reports (2014) 15: 489–507), Boris (Boris Umylny et al. Journal of Cellular Biochemistry 102:110–121 (2007)) and Muszewska (Muszewska et al. Scientific Reports (2019) 9:4307).
Regarding claims 1, 3 and 46, Hannon teaches the use of single-stranded RNA constructs (natural or modified), known herein as "piRNA," to modulate target gene expression [0015]. Hannon teaches that production of piRNA oligonucleotides can be carried out by chemical synthetic methods or by recombinant nucleic acid techniques [0064, 0163]. Hannon teaches that the piRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of a genomic sequence to cause down-regulation of transcription at the genomic level, or an mRNA transcript for a gene to be inhibited (i.e., the "target" gene) [0064]. Hannon teaches that because the piRNA need only be sufficiently similar to natural RNA, it is able to tolerate sequence variations that might be expected due to genetic mutation, strain polymorphism (which includes single nucleotide polymorphisms (snps)) or evolutionary divergence [0064]. Hannon teaches that a transposon-rich piRNA cluster gives rise to a variety of piRNAs [0098]. Hannon teaches that a random arrangement of transposon fragments (i.e., transposon remnants) would initially produce a mixture of sense and antisense piRNAs (i.e., an isolated single-stranded synthetic nucleic acid comprising a complementary sequence that targets a transposon remnant sequence that is no longer capable of transposition) that inactivates the target gene [0098-0099]. Hannon teaches that the piRNA can be on a viral vector [0021]. Hannon teaches that the the piRNA sequence generally will be substantially identical (although in antisense orientation) or complementary to the target gene sequence (i.e., aligns with high identity, wherein high identity is defined as having greater than 75% homology). Hannon teaches using piRNA to identify compounds that modulate a pathway, thereby teaching that piRNAs can align within a functional gene pathway [claim 34].
While Hannon teaches that the piRNAs are able to tolerate sequence variations that might be to strain polymorphism (which includes single nucleotide polymorphisms (snps)), Hannon does not specifically teach that the transposon remnant target contain single nucleotide polymorphisms rending unique a set of genes sharing gene loci with the snp-containing sequence being targeted. Hirose does not specifically teach that piRNAs align to a regulatory region of one or more other genes within the functional gene pathway and/or the gene network.
Hirose teach PIWI-interacting RNAs (piRNAs) that are complementary to genomic regions in which transposon-related repetitive sequences are encoded [pg. 493, last paragraph]. Hirose teach that piRNAs play a pivotal role in protecting the germline genome from transposons that are potential threats to genome integrity in living organisms [pg. 493, last paragraph]. Hirose teach that piRNAs arise from piRNA clusters, where multiple copies of transposon remnants (also known as transposable element (TE) remnants that are DNA sequences derived from transposable elements that have become inactive, no longer capable of transposition) reside in sense and antisense orientation [pg. 493, last paragraph], thereby teaching that piRNAs can be complementary and align to transposon remnants which are no longer capable of transposition. Hirose also teach that piRNAs act as guide molecules to silence complementary transposon RNAs either by post-transcriptional cleavage or by transcriptional silencing [pg. 494, col. 1, para 1]. Hirose teaches that the resultant piRNA-containing RISC acts as an RNP machinery and silences transposon RNAs by post-transcriptional cleavage and transcriptional silencing where the RISC mediates RNAi by cleaving perfectly complementary target RNAs (i.e., piRNA aligns with 100% identity to target) [Fig. 2]. Hirose teach that loss of piRNAs not only stabilizes transposon RNAs but also reduces repressive epigenetic marks and activates transcription at transposon loci, thereby teaching that piRNAs aids in the repression of transposon mediated gene activation [pg. 494, last paragraph].
Boris teach that the short-interspersed repeat elements (SINEs) of Alu ad B1 (i.e., a type TE; non-autonomous retrotransposons that are short, non-coding sequences), which are derived from the 7SL RNA gene, are found all over the human and mouse genome, respectively [abstract]. Boris teach that over 98% of 923,277 Alus and 365,377 B1s examined were unique when queried at full length [abstract]. Boris teach searching the entire human and mouse genome for Alus and B1s using BLAST [pg. 113, col. 2, para 3 – pg. 114, col.1, para 2]. Boris teach that even at 50% of their lengths, greater than 97% of Alus and 73% of B1s were identified as single-copy sequences [pg. 117, col. 1, para 2].
Muszewska teach that transposon elements (TEs) and TE fragments (i.e., remnants) are inserted into genic regions and are found in proximity of genes on either side, being equally ubiquitous downstream and upstream of genes [pg. 3, para 10]. Muszewska teach that more compact genomes host more remnant TEs inserted into genes as compared to genomes with greater non-genic space [pg. 3, para 10]. Muszewska teaches a remnant LTR retrotransposon (i.e., transposon remnant) that is inserted into a promoter region (i.e., a transcriptional regulatory region (regarding claims 1 and 3)) of a MFS1 transporter gene thereby inducing gene overexpression and enhancing fungicide resistance (i.e., functional pathway) [pg. 2, para 1-2]. Overall, Muszewska teach that TE remnant sequences can exist in one or more other genes within the functional gene pathway and/or the gene network, and they can exist in regulatory regions of a gene.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to use BLAST as taught by Boris to screen for unique transposon remnants that contains single nucleotide polymorphisms and generate a piRNAs that targets the remnants as taught by Hannon and Hirose. One of ordinary skill would be motivated to make the modification for the advantage of protecting the germline genome from unique transposons that are potential threats to genome integrity, by mediating a reduction in gene activation, as taught by Hannon and Hirose. One or ordinary skill would have a reasonable expectation of success since Boris teach that there can be over 800,000 unique single copy transposon elements in a given part of a genome and Hannon and Hirose teaches the ability to target any one of these transposon element using piRNAs for protecting germline genome.
Regarding claim 5, Hannon that the piRNAs may include modifications to either the phosphate-sugar backbone or the nucleoside [0065]. Hannon teaches that the oligonucleotides can be derivatized or chemically modified by binding to a conjugating agent to facilitate cellular uptake [0175]. Hannon teaches certain protein carriers can also facilitate cellular uptake of oligonucleotides, including nuclear proteins possessing signals for transport to the nucleus [0176].
Regarding claim 6, the limitation “wherein the given functional pathway is selected from the group consisting of: epithelial to mesenchymal transition pathway, phospholipid signaling pathway, myogenesis pathway, stress-mediated fat metabolism pathway, CD4+ T cell activation and HIV binding pathway, and a Parkinson's Disease-associated pathway” is directed to the functional pathway of the gene and does not distinguish the claimed synthetic nucleic acid from the prior art as taught above.
Regarding claim 43, “wherein the transposon remnant sequence is 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” is directed to the transposon remnant sequence and does not distinguish the claimed synthetic nucleic acid from the prior art as taught above. Furthermore, Hirose teaches that transposons (i.e., transposon remnants) are mobile genetic elements [pg. 493, last paragraph] and does not teach that the remnants function as a transcription factor binding site, primer binding site, small RNA, miRNA, piRNA, siRNA, or eRNA of previously defined function or coding sequence.
Regarding claim 44, Hirose teaching of a piRNA [pg. 493, last paragraph] is a teaching of an RNA based synthetic nucleic acid.
Claims 4 is rejected under 35 U.S.C. 103 as being unpatentable over Hannon (US 2009/0062228 A1) in view of Hirose (Hirose et. al. EMBO Reports (2014) 15: 489–507), Boris (Boris Umylny et al. Journal of Cellular Biochemistry 102:110–121 (2007)) and Muszewska (Muszewska et al. Scientific Reports (2019) 9:4307) as applied to claim 1, and further in view of Kennedy (Kennedy et al. BMC Bioinformatics volume 12, Article number: 130 (2011)).
The teachings of Hannon, Hirose, Boris and Muszewska are discussed above as applied to claim 1 and similarly apply to claims 4. Hannon, Hirose, Boris and Muszewska do not teach wherein the high identity is defined based on high identity BLAT2013 alignment, or other "in silico" genomic alignment algorithm.
Kennedy teaches a homology-based approach for the automatic identification of TEs in genomes using multiple sequence alignment programs such as BLAST [abstract]. Kennedy teaches the alignment approach using BLAST [pg. 3, col. 2, para 3]. Kennedy teaches that this a way to identify and annotate TEs effectively and quickly thereby allowing researchers the ability to quickly produce high-quality consensus TEs [pg. 10, col. 1, para 2].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention that the synthetic nucleic acid as taught and suggested by Hannon, Hirose, Boris and Muszewska could be identified by BLAST of Kennedy. One of ordinary skill would be motivated to align the sequences in order to quickly produce high-quality consensus nucleic acids.
Response to Arguments
Applicant's arguments, see pgs. 4-5 filed 1/12/2026, with respect to the rejection of claims 1-3, 6 and 43-44 under 35 U.S.C. § 112(a) have been fully considered and but they are not persuasive. The amendments to the claims do not overcome the rejection as the claims are still directed to a genus of synthetic nucleic acid molecules that target a transposon remnant that is no longer capable of transposition and that contains snps that were dispersed during transposition. The state of the art regarding transposon remnants at the time of the invention was that not all transposon remnants were known. Hayward (Hayward and Gilbert. Current Biology Volume 32, Issue 17, 12 September 2022, Pages R904-R909; post filing art) teaches that many transposable elements still remain unknown [pg. R907, col. 3]. Therefore, applicants are still not in possession of the genus of all synthetic nucleic acid molecules that target a transposon remnant that is no longer capable of transposition and that contains snps that were dispersed during transposition.
Applicant's arguments, see pgs. 4-5 in the office action filed 3/24/2025, with respect to the rejection of claims 1-3, 6 and 43-44 under 35 U.S.C. § 103 have been fully considered and but they are not persuasive. Applicants argue that nothing in Hirose discloses or suggests that the piRNAs target transposon remnant sequences. Hirose teaches that piRNAs are complementary to genomic regions in which transposon-related repetitive sequences are encoded, thereby teaching that they can target transposon-related repetitive sequences (from which transposon remnants arise). In addition, Hirose teaching that piRNAs arise from a set of genomic loci where transposon remnants arise is a teaching that they are complementary to these regions and a skilled artisan would know that this means that they are therefore capable of targeting those regions. Furthermore, a new rejection is set forth above that teaches that piRNAs can be produced to target transposon remnants.
Applicants argue that the office action contends that Boris or Muszewaska alone cures the deficiency of Hirose not teaching that the transposon remnant contain single nucleotide polymorphism that renders unique a region of genes sharing the sequence being targeted. Applicant’s arguments do not address the merits of the rejection. It is the combination of teachings from HIrose, Boris and Muszewaska that cures the deficiency of Hirose.
Conclusion
No claims 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.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637