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 status
In the reply filed 13 July 2026, Applicant has cancelled claims 1-17 and included new claims 18-33. Applicants disclose in the remark that previous Claim 1 is replaced with new claim 18, which has support, inter alia, at paragraph [0112] of the specification. Parallel changes are reflected in claims 19-33 which replace claims 2-16. After amending the claims as set forth above, new claims 24-33 correspond to previously withdrawn claims.
Therefore, 18-33 are pending.
Election/Restrictions
Applicant previously elected without traverse of Group I, claims 18-23, drawn to method of obtaining a cell in the reply filed on 19 February 2026.
Claims 24-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Since applicants have received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 24-33 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03
Claims 18-23 are under current examination.
Priority
This application was filed 09/01/2023 and is a 371 application of PCT/JP2022/008713 filed on 03/02/2022, which claims benefit to the foreign application JP2021-033658 filed on 03/03/2021.
To meet the foreign priority under 35 U.S.C. 119(a) -(d) prior to declaration of an interference, Applicant has submitted a certified English translation of the foreign application in the reply filed on 07/13/2026 is acknowledged.
Thus, the earliest possible priority for the instant application is 03/03/2021.
Withdrawn Claim Rejections
Applicant amends claim 18 to recite " wherein, in the (i) to (iii) above, the selected cell does not comprise a selection marker gene or a site-specific recombination sequence at the target sequence," therefore, breadth of a claim 18 has changed and which was not taught Takeda (US20080104723A1) or Masumoto (JP 2018-191561A). Therefore,
the prior rejection of claim 18-22 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Takeda et al., (US20080104723A1, cited in IDS filed 09/01/2023; hereinafter “Takeda”) is withdrawn.
the prior rejection of claim 18-23 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Masumoto et al., (JP2018191561A, attached the EPO translated copy; cited in IDS filed 09/01/2023; hereinafter “Masumoto”) is withdrawn.
New 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 18-22 are newly rejected under 35 U.S.C. 103 as being unpatentable Takeda et al., (US20080104723A1, cited in IDS filed 09/01/2023; hereinafter “Takeda”), in view of Economides et al. (US20070275466A1; Pub. Date: Nov. 29, 2007; cited in PTO892; hereinafter “Economides”). The new rejection is necessitated by applicant’s claim amendments.
Examiner’s claim interpretation: Amended claim 18 recited “a nucleotide sequence having 50% or more sequence identity to any one of the nucleotide sequences of the retrotransposons in the genomic DNA,” For the sole purpose of compact prosecution, examiner interpreted that the retrotransposon or retrotransposon-like sequence may have a non-natural nucleotide sequence (see SPEC [0035]). Therefore, the retrotransposon or retrotransposon-like sequence can be appropriately designed and synthesized by those skilled in the art.
Regarding claims 18-21, Takeda describes a method of modifying a genome in a cell, said the cell comprises genomic DNA, wherein method comprising the steps of: A) providing a nucleic acid construct containing an LTR-type retrotransposon and a promoter; B) introducing said nucleic acid construct into said cell; C) culturing said cell for a predetermined period of time; and D) selecting a cell with a genome that has been modified by said nucleic acid construct. Takeda further states the following: that the aforementioned nucleic acid construct contains a foreign gene located in an operable manner in the aforementioned retrotransposon; that the aforementioned selection is achieved by the expression of said foreign gene; and that the aforementioned cell belongs to the same species as that of the natural host of the retrotransposon (claims 32, 35, 43 and 48). Takeda further states the nucleotide sequence to be introduced in the modifying genome preferably at least about 98% identity sequence identity to any one of the nucleotide sequences of the retrotransposons. [0285]-[0286].
Takeda states the following: that any sequence can serve as the retrotransposon sequence; that a variety of nucleic acid sequences can be inserted into the portion that is to be sandwiched by retrotransposon sequences; that when performing genome modification, not only a modification in the vicinity of the target, but also the effect of said modification is also attained, namely, that the modification can be inserted into the entire genome in an exhaustive manner or universal manner [0109], [0111], [0114], [0236].
Takeda teaches generation and selection of genetically modified ES cells using homologous recombination and selectable marker genes, including neomycin-resistance-based positive selection and HSV-TK-based negative selection. Takeda further teaches Cre-loxP-mediated site-specific recombination in genetically modified ES cells ([0212]-[0214] of Takeda). However, Takeda does not expressly teach that the finally selected cell lacks both a selectable marker gene and a site-specific recombination sequence at the target sequence. Rather, Takeda’s disclosed targeting strategies employ selectable marker genes and, in the Cre-loxP embodiment, site-specific loxP recombination sequences at the modified locus ([0217] of Takeda). However, Takeda alone does not teach the amended claim limitation “the selected cell does not comprise a selection marker gene at the target sequence.”
Economides teaches genetically modifying ES cells using a targeting vector and subsequently removing the selectable marker cassette from appropriately targeted ES cells using a site-specific recombinase (abstract, [0051], [0081] of Economides). Economides further teaches negative selection of cells in which the selection cassette has not been removed, thereby providing a cell population that lacks the selection cassette while retaining the desired genetic modification ([0077]-[0078] of Economides).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention to modify the homologous-recombination method of Takeda by removing the selectable marker cassette after selection of the desired recombinant cells, as taught by Economides, in order to retain the desired targeted modification while eliminating the selectable marker sequence ([0078] of Economides). A person of ordinary skill in the art would have had a reasonable expectation of success because Economides expressly teaches successful removal of the selectable cassette from targeted ES cells and subsequent selection of cells lacking that cassette.
Regarding claim 22, Takeda teaches that the nucleotide sequence to be newly introduced is identical to any one of the nucleotide sequences of the retrotransposons in the genomic DNA [0284].
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 18-23 are newly rejected under 35 U.S.C. 103 as being unpatentable Masumoto et al., (JP2018191561A, attached the EPO translated copy; cited in IDS filed 09/01/2023; hereinafter “Masumoto”), in view of Economides et al. (US 2007/0275466A1; Pub. Date: Nov. 29, 2007; cited in PTO892; hereinafter “Economides”). The new rejection is necessitated by applicant’s claim amendments.
Regarding claims 18-23, Masumoto discloses a method of inserting foreign DNA into two or more sites of genomic DNA, said method comprising the insertion of a foreign DNA sequence into two or more copies of a nucleotide sequence of at least 200 bp contained in genomic double-stranded DNA wherein, in a host cell with two or more copies of said genomic double-stranded DNA containing said nucleotide sequence of at least 200 bp, (1) said genomic double-stranded DNA and (2) a donor DNA comprising both a nucleotide sequence homologous with said nucleotide sequence of at least 200 bp or a partial sequence thereof and a foreign DNA sequence are brought into contact with a nuclease that binds specifically to a selected target sequence within the nucleotide sequence of at least 200 bp and cleaves the DNA in said target sequence, thereby allowing homologous recombination between the nucleotide sequence of at least 200 bp in said genomic double-stranded DNA and the homologous sequence or partial sequence thereof contained in said donor DNA, and resulting in the insertion of the foreign DNA sequence into said two or more copies of the nucleotide sequence of at least 200 bp in the genomic double-stranded DNA, and the homologous nucleotide sequence has both sufficient sequence identity and length to bring about homologous recombination if the DNA in the target nucleotide sequence of at least 200 bp in the genomic DNA is cleaved. Masumoto further states that said nucleotide sequence of at least 200 bp is a retrotransposon (100% identity to the retrotransposons) (claims 1-2, and 11, [0018] of English translation copy). Moreover, Masumoto states that said donor DNA can also contain an optional marker gene for selecting a transformant wherein the foreign DNA has been inserted into the genome ([0049] of translated copy).
However, Masumoto does not teach the amended claim limitation “the selected cell does not comprise a selection marker gene at the target sequence.
Economides teaches genetically modifying ES cells using a targeting vector and subsequently removing the selectable marker cassette from appropriately targeted ES cells using a site-specific recombinase (abstract, [0051], [0081] of Economides). Economides further teaches negative selection of cells in which the selection cassette has not been removed, thereby providing a cell population that lacks the selection cassette while retaining the desired genetic modification ([0077]-[0078] of Economides).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention to modify the homologous-recombination method of Masumoto by removing the selectable marker cassette after selection of the desired recombinant cells, as taught by Economides, in order to retain the desired targeted modification while eliminating the selectable marker sequence ([0078] of Economides). A person of ordinary skill in the art would have had a reasonable expectation of success because Economides expressly teaches successful removal of the selectable cassette from targeted ES cells and subsequent selection of cells lacking that cassette.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicants’ arguments filed on 13 July 2026 are acknowledged.
Applicants argue that Takeda introduces a nucleic acid construct comprising an LTR-type retrotransposon, a promoter, and a foreign gene operably arranged within the retrotransposon, and selects cells by expression of that foreign gene. Therefore, applicant argues that the integrated region at the target necessarily retains the promoter and the foreign gene; it does not "consist of' a retrotransposon / retrotransposon-like sequence, and the selected cell comprises a foreign gene functioning as a selection marker at the target. Applicant further argues that Takeda' s "[Symbol font/0xB3]98% identity" passage concerns the retrotransposon portion only and does not eliminate the promoter or foreign gene. Takeda therefore fails to disclose amended step (i) and the new wherein limitation and does not anticipate claims 18-22. See remark p. 9 1st ¶.
To the extent Applicant relies on the presence of additional promoter or foreign gene sequences in Takeda’s construct to distinguish the claimed nucleotide-sequence-identity limitation, such additional components do not negate Takesa’s express disclosure of the recited retrotransposon sequence having required degree of sequence identity. Although claims are given their broadest reasonable interpretation in light of specification, the limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). However, the newly added limitation requiring that the selected cell does not comprise a selection marker gene at the target sequence must be separately addressed. Takeda discloses that the retrotransposon portion has at least 98% sequence identity does not, by itself, establish the absence of a selectable marker gene or site-specific recombination sequence at the target sequence [0285]-[0286]. Accordingly, Takeda's sequence identity disclosure is sufficient to meet the recited “50% or more sequence identity” limitation, but a separate factual basis is required to establish amended claim limitation. Therefore, Applicant arguments have been fully considered but they are not persuasive.
Masumoto inserts a foreign DNA sequence into two or more retrotransposon copies via nuclease cleavage and homologous recombination, using a donor DNA comprising a homology arm and a foreign DNA sequence (and, optionally, a selection marker gene). The resulting modified region therefore contains the inserted foreign DNA (and, in the marker embodiment, a marker gene); it does not "consist of' a retrotransposon / retrotransposon-like sequence. Masumoto's "100% identity" statement concerns the genomic retrotransposon target, not the inserted payload. Masumoto therefore fails to disclose amended step (i) (and, in the marker embodiment, the wherein limitation) and does not anticipate claims 18-23. See remark p. 9 2nd ¶.
In response to applicant arguments that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the inserted foreign DNA (and, in the marker embodiment, a marker gene) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In here, the homologous nucleotide sequence of Masumoto has both sufficient sequence identity and length to bring about homologous recombination if the DNA in the target nucleotide sequence of at least 200 bp in the genomic DNA is cleaved. Masumoto further states that said nucleotide sequence of at least 200 bp is a retrotransposon (100% identity to the retrotransposons) (claims 1-2, and 11, [0018] of English translation copy). Therefore, Masumoto's 100% identity of the retrotransposon portion reads on the claim limitation of “introducing a nucleotide sequence having 50% or more sequence identity to any one of the nucleotide sequences of the retrotransposons in the genomic DNA.”
Applicant argues that the invention's purpose - embedding a covert, practically-undetectable identifier indistinguishable from the genome's many native transposons - is achieved precisely because the modified region consists only of a retrotransposon-like sequence and carries no artificial marker. See remark p. 10 1st ¶.
Applicant arguments have been fully considered but they are not persuasive. In response to applicant arguments that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., carries no artificial marker) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are 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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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