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
This action is written in response to applicant’s correspondence received 02/13/2026. Claims 4-10, 12-13 are currently pending. Claims 4-10 are withdrawn from prosecution as being drawn to nonelected subject matter. Accordingly, claims 12-13 are examined herein. The restriction requirement mailed on 12/16/2025 is still deemed proper. Applicant's elected Group IV without traverse in the reply filed on 02/13/2026.
Election/Restrictions
Applicant's election without traverse of Group IV (claims 12-13) in the reply filed on 02/13/2026 is acknowledged. Applicant’s election of the species “DNA pathway” for claim 12 and the species “CNV sequence(s)” for claim 13 is acknowledged.
Claims 4-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being
drawn to a nonelected invention Group II, there being no allowable generic or linking claim. The restriction requirement mailed on 12/16/2025 is still deemed proper and is therefore made FINAL.
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. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in CHINA 202110089068.1 on 01/22/2021. This application is a 371 of PCT/CN2021/134710 filed on 12/01/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because: It uses 183 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 12 and 13 are broadly objected to because it recites numerous elements without properly setting forth the indefinite article ("a" or "an") for initial introduction and the definite article ("the" or "said"), or other minor informalities. Although the scope of the claim is generally clear, it would benefit from the following edits to remove the grammatical inaccuracies to improve clarity of the record.
The edits for the following line numbers of claim 12 are recommended:
Line 1, “the vector system” should be “a vector system” for initial introduction;
Line 2, “the DNA pathway” should be “a DNA pathway” for initial introduction;
Line 3, “DNA sequence(s)” should be “a DNA sequence” and “the genome” should be “a genome” for initial introduction; “a DNA sequence” is important for providing clear antecedent basis for “the DNA sequence” in claim 13 based on the disclosure in specification (Page 7, last 6 lines), and for resolving confusion with “a segment of DNA sequence” in line 8.
Line 5, “the gene transcription framework” should be “a gene transcription framework” for initial introduction; “characterized in” should be “characterized by” because "by" correctly identifies the specific attribute that defines the subject;
Line 6, “target site” should be “a target site” for initial introduction;
Lines 7, 13, 16, 19-22, “target site” should be “the target site” referring to “a target site”;
Line 8, “DNA sequence” should be “DNA” to avoid confusion with “a DNA sequence” in line 3;
Line 11, “the transcription” and “the transformation” should have “the” replaced with “a” for initial introduction;
Line 23, “the target site of…” should be “the target site for the sequence to be inserted into”.
The following edit for claim 13 is recommended:
Line 1, “characterized in” should be “characterized by” because "by" correctly identifies the specific attribute that defines the subject.
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.
Claim 12-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter recited in 35 U.S.C. §101 (process, machine, manufacture, or composition of matter) because they merely recite a use without any active, positive steps delimiting how the use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP §2173.05(q).
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.
Claims 12-13 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.
Regarding claims 12-13, both are “Use” claims. It is unclear what are the metes and bounds
of the broad terms “a vector system mediated by DNA pathway for insertion, deletion, substitution of DNA sequence(s) in any region of a genome”. Also unclear is how the vector system relates to the recited “for insertion, deletion, substitution of DNA sequence(s) in any region of a genome” without setting forth any step involved in the process. see MPEP §2173(q).
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.
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 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Rubens (WO 2020/047124 A1, published on 03/05/2020, filed on 08/28/2019), as evidenced by Fujiwara
(APE-type non-LTR retrotransposons of multicellular organisms encode virus-like 2A oligopeptide sequences, which mediate translational recoding during protein synthesis. Mol Biol Evol. 2013 Aug;30(8):1955-65), in view of Fadloun (WO 2016/030501 A1, published on 03/03/2016, filed on 08/28/2015), further in view of Fujiwara (2013; citation above) and Wei (Human L1 retrotransposition: cis preference versus trans complementation. Mol Cell Biol. 2001 Feb;21(4):1429-39Mol Cell Biol. 2001 Feb;21(4):1429-39), as evidenced by Porokhovnik (Dosage effects of human ribosomal genes (rDNA) in health and disease. Chromosome Res. 2019 Mar;27(1-2):5-17).
Regarding claim 12,
Regarding the claim limitation of “vector system”:
Rubens (2020) teaches a nucleic acid vector-based (Page 26, line 30; Page 27, lines 1 & 3) Gene Writing genome editing system, i.e. a vector system (Page 40, line 16; Figure 1).
The recitation by Rubens, “… for targeting, editing, modifying or manipulating a DNA sequence … at one or more locations in a DNA sequence in a cell, tissue or subject …” (Page 47, lines 14-17) matches the claim limitation “for insertion, deletion, substitution of DNA sequence(s) in any region of the genome”, even though it is only intended use and carries no patentability weight.
Rubens also teaches that “In some embodiments, a nucleic acid described herein (e.g., an RNA encoding a Gene Writer polypeptide, or a DNA encoding the RNA)” (Page 57, lines 3-4), which confirms that, at least in some embodiments, the vector system of Rubens is mediated by a DNA pathway, and that it comprises at least one vector.
Regarding the claim limitation of 1) one or more “gene transcription framework”:
Rubens teaches “In some embodiments, the object sequence may contain a non-coding sequence. For example, the template RNA may comprise a promoter or enhancer sequence…. In some embodiments the promoter is an RNA polymerase I promoter, RNA polymerase II promoter, or RNA polymerase III promoter” (Page 542, lines 20-24; Page 543, line 1).
Rubens further teaches:
“4. A system for modifying DNA comprising:
(b) a template RNA (or DNA encoding the template RNA) , see Rubens, Figure 1.
Rubens also teaches in claims 19-20: “… the template RNA comprises … 100% identity to a target DNA strand, at the 5' end ... at the 3' end of the template RNA.” (Page 598; Fig. 1), which is the same of “an upstream sequence” and “a downstream sequence of target site”. Since these homology arms are located on the same strand of RNA or DNA molecule and are arbitrary design choices, at least some embodiments of Rubens are directly connected in the corresponding target gene sequence in the genome. Figure 1 of Rubens shows the homology-directed insertion using the Gene WriterTM, and the transgene retro-insertion does not result in a spacer being displaced between homology arms in the target site, indicating that the upstream and downstream homology arms of the target site were connected directly prior to the retro-insertion.
Regarding the claim limitations of 3) one or more long interspersed element(s), and/or ORF1p coding sequence(s) and/or ORF2p coding sequence(s):
Rubens teaches: “In certain embodiments, the elements of the Gene Writer™ gene editor polypeptide can be derived from sequences of non-LTR retrotransposons, …” (Page 49, lines 17-19), and lists numerous species of long interspersed nuclear elements (LINEs) in Table 2 on Pages 57-136, including CRE, R1, R2, R4, HERO, NeSL, Tx1, etc., many of which encode nuclease and reverse transcriptase as evidenced by Fujiwara (2015; Page 1, right column, line 8; Figure 2 on page 3).
Regarding the claim limitations of 2) one or more short interspersed element(s) and/or partial short interspersed element(s).
Rubens does not teach the claim limitation of 2) one or more short interspersed element(s) and/or partial short interspersed element(s).
However, Fadloun (2016) teaches synthetic Alu Retrotransposon vectors for gene therapy using Alu elements, which are “short interspersed nuclear elements (SINEs) that use the reverse transcriptase and nuclease encoded by long interspersed nuclear elements (LINEs) to integrate into the host genome” (Page 14, lines 11-14). Fadloun does not teach combining LINEs and SINEs in the same vector system because the invention is directed to target gene insertion in cancer cells that already have higher than normal expression levels of LINEs.
However, Fujiwara teaches that LINEs “are in general 4 to 7 kb long” and “SINEs are nonautonomous retrotransposons of 100 to 500 bp that do not encode proteins” (Page 1, right column, 1st ¶, lines 10, 12-14). The drastic difference in RNA length supports the advantage in using SINEs for greater retro-insertion efficiency and offers flexibility in vector design for cargo capacity considerations. This is especially impactful in view of Wei (2001)’s teaching of the cis-preference of LINEs in that LINE-encoded ORF proteins predominantly mobilize the RNA that encodes them…, not the other copies of LINE RNAs already inserted in the genome, but these proteins can act in trans to promote retrotransposition of SINEs such as Alu elements (Page 1429, Abstract). This provides the opportunity to incorporate SINEs in the vector system on a separate vector because the capacity for a transgene is very limited in the same/cis vector that comprise the LINE RNA due to its large size, however, a separate SINE vector in the same vector system would have a much larger capacity to accommodate transgenes because it does not require encoding its own ORF proteins, and SINEs can still compete for the LINE-encoded ORF proteins in proximity and successfully complete retro-insertion to integrate a larger transgene efficiently.
It would have been obvious for persons having ordinary skill in the art (PHOSITAs) before the effective filing date to have modified the vector system of Rubens by combining the short length, larger cargo capacity, and efficient genomic integration characteristics of the Alu element vector, taught by Fadloun, with the Gene Writer TM vector system that comprise an ORF-encoding LINE, based on the motivation to enhance the genome editing efficiency and broaden its cargo capacity, and would have arrived at the claimed invention based on the teachings, strategies, and motivations from Rubens, Fadloun, Fujiwara, and Wei.
Regarding claim 13, Rubens further teaches that “…retrotransposases described herein can insert heterologous nucleic acid in an endogenous site in the genome, such as the rDNA locus (see, e.g., Example 7)” (Page 48, lines 10-12; Pages 571-573), and that “Figure 9 shows a ddPCR evaluation of copy number variation … in human cells across transfection conditions” (Page 41, lines 15-16). Since the rDNA locus is well known in the art to vary across individuals, and is a well characterized safe harbor site in the art (Rubens, 2020; Page 545, lines 17-20) for gene insertions based on the following recitations: “In some embodiments the Natural Harbor™ site is ribosomal DNA (rDNA). In some embodiments the Natural Harbor™ site is 5S rDNA, 18S rDNA, 5.8S rDNA, or 28S rDNA” (Page545, lines 17-20)…”, despite the CNV sequence status of rDNAs as evidenced by Porokhovnik (2016; see full citation above) demonstrating that there is a clear association between certain disease development and the dosage of rDNA gene copy numbers in different individuals (Page 14, right column, 2nd ¶, last 7 lines). Hence, Rubens teaches that the Gene Writer™ vector system can perform insertion, deletion, substitution of CNV DNA sequence(s) in the genome, such as rDNA CNV sequences.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Delphinus D. Yu whose telephone number (571) 272-1576. The examiner can normally be reached Mon-Thr 7:30am to 4:30pm Fri 10am to 2pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil P Hammell can be reached on (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DELPHINUS DOU YI YU/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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