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 .
This action is in response to the amendment filed 06/02/2026, in which claims 55-96 were cancelled and claims 97-115 were newly added. Claims 97-115 are currently pending and under examination.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn. This action is FINAL.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant's claim for foreign priority based on the applications filed as KR 10-2021-0114750 on 08/30/2021, KR 10-2021-0092056 on 07/14/2021, KR 10-2021-0085474 on 06/30/2021, KR 10-2021-0085473 on 06/30/2021, KR 10-2021-0050497 on 04/19/2021, KR 10-2021-0049348 on 04/15/2021, KR 10-2021-0016788 on 02/05/2021, KR 10-2021-0013263 on 01/29/2021, KR 10-2020-0159920 on 11/25/2020 and KR 10-2020-0120399 on 09/18/2020.
It is noted, however, that applicant has not filed an English translation of the certified copies as required by 37 CFR 1.55.
All claims are given the filing date of 09/17/2021.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 12/22/2025, 03/30/2026 and 08/03/2026 have been received and all references have been considered.
Specification
The substitute specification filed 06/02/2026 has not been entered because it does not conform to 37 CFR 1.125(b) and (c) because: it is not accompanied by a statement of no new matter.
Therefore, the previous objection to the specification is maintained in view of the substitute specification not being entered. The previous objection is as follows:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (Paragraphs [931, 966, 975 and 999]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
The previous objection to claims 62-96 have been withdrawn in view of cancelation of the claims by Applicant in the amendments filed on 06/02/2026.
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 97-115 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. This is a NEW Rejection necessitated by the amendment to the claims filed on 06/02/2026.
Claim 97 is drawn to a genus of cytosine deaminase. The rejected claims thus comprise a genus of cytosine deaminase that encompass the “first split derived from a cytosine deaminase or a variant thereof,” and “a second split derived from a cytosine deaminase or a variant thereof”. The number and type of mutations relative to the recited sequences is not limited in any way, yet the variant must be capable of functioning as a cytidine deaminase within a fusion protein for genome editing within a cell.
Claim 101 depends from claim 97 and recites, “wherein the adenine deaminase is a tRNA-specific adenosine deaminase (TadA) or a variant thereof.” Thus, the claim encompasses any adenine deaminase sequence that has been derived by any number of changes relative to any TadA, as well as any orthologs of TadA or the derivatives. The derivatives and orthologues thereof must be capable of functioning within a fusion protein for genome editing within a cell.
Claim 102 depends from claim 97 and recites, “wherein the cytosine deaminase is derived from a double-stranded DNA deaminase (DddA) or an orthologue thereof.” Thus, the claim encompasses any cytosine deaminase sequence that has been derived by any number of changes relative to any DddA, as well as any orthologs of DddA or the derivatives. The derivatives and orthologues thereof must be capable of functioning within a fusion protein for genome editing within a cell.
Claim 103 depends from claim 97 and specifies that the one or more substitutions within SEQ ID NO: 1. The claim encompasses variants where one or more of the recited amino acid positions is substituted with any other amino acid. The variant must be capable of functioning as a cytidine deaminase within a fusion protein for genome editing within a cell.
Claim 107 is drawn to a genus of cytosine deaminase. The rejected claims thus comprise a genus of cytosine deaminase that encompass “a non-toxic full-length variant of a cytosine deaminase”. The number and type of mutations relative to the recited sequences is not limited in any way, yet the variant must be capable of functioning as a cytidine deaminase within a fusion protein for genome editing within a cell while remaining non-toxic.
Claim 111 depends from claim 107 and recites, “wherein the adenine deaminase is a tRNA-specific adenosine deaminase (TadA) or a variant thereof.” Thus, the claim encompasses any adenine deaminase sequence that has been derived by any number of changes relative to any TadA, as well as any orthologs of TadA or the derivatives. The derivatives and orthologues thereof must be capable of functioning within a fusion protein for genome editing within a cell.
Claim 112 depends from claim 97 and recites, “wherein the cytosine deaminase is a DddA or an orthologue thereof.” Thus, the claim encompasses any cytosine deaminase sequence that has been derived by any number of changes relative to any DddA, as well as any orthologs of DddA or the derivatives. The derivatives and orthologues thereof must be capable of functioning within a fusion protein for genome editing within a cell while remaining non-toxic.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes specific variants of the full-length cytosine deaminase as SEQ ID NOs: 12-22 that were proved to be non-toxic variants of the wild-type sequence for use in the fusion protein with a programmable DNA binding protein [0230-0243, 0251-0252 and 0255-0261]. The sequences provided in the specification as SEQ ID NOs: 12-22 are variants of SEQ ID NO: 1 with specific residue mutations at different amino acid positions such as Al341D KRKKA (SEQ ID No: 12), AAAAA (SEQ ID No: 13), AAAAK (SEQ ID No: 14), AAKAA (SEQ ID No: 15), AAKAK (SEQ ID No: 16), KAAAA (SEQ ID No: 17), El347A (SEQ ID No: 18), GSVG (SEQ ID No: 19), SSVG (SEQ ID No: 20), GSAG (SEQ ID No: 21) and GSVS (SEQ ID No: 22), respectively [230, 232, 234, 236, 238, 240, 242, 251, 256 258, and 260]. The specification also envisions specific adenine deaminases such as APOBEC1, AID and tadA, specifically the sequence of ABE 8e is provided as SEQ ID NO: 458 [0319 and 0468-0469]. In regards to the split-DddAtox halves, the specification teaches DddAtox is cytotoxic, and thus, in order to avoid toxicity in host cells, DddAtox is split into two inactive halves, each of which is fused to a DNA-binding protein in a DddA-derived cytosine base editor (DdCBE) and wherein a functional deaminase is reassembled at a target DNA site, when two inactive halves are brought together by the DNA-binding protein [7]. The instant specification also teaches the DddAtox split system has many limitations in experiments such as many Gl397-split DddAtox variants, containing interface mutations such as C1376A, Ml390A and Fl412A, failed to induce C-to-T conversions in the spacer region between the two TALE-binding sites, even when combined with the wildtype partner, suggesting that these mutants cannot interact with other wildtype DddAtox half nearby at the target site [8 and 1007]. In regards to the full-length toxicity of DddA, the specification describes that since DNA is negatively charged, it binds to the positively charged amino acid of a protein and by substituting the positively charged amino acid with an amino acid that is not charged, binding force of DddAtox to DNA is weakened, thus reducing or eliminating cytotoxicity which results in a non-toxic combination resulting from substitution of a positively charged amino acid with a non-polar amino acid enables cloning using E. coli to afford full-length DddA [220]. The specification teaches that the results showed a limited number of non-toxic full-length DddA variants with reduced affinity for dsDNA (AAAAA), attenuated deaminase activity (E1347A and possibly GSVG), or reduced cytotoxicity (GSVG) that can be fused to dCas9 or nCas9 to create novel base editors with altered editing windows [1040]. Although a description is provided of specific variants that were capable of functioning comparable to the wild-type versions of the cytosine and adenine deaminases, no description is provided of all the variants that retain the original enzymatic function (e.g., adenosine deaminase or cytosine deaminase) or that switch from adenosine deaminase to cytosine deaminase function, or vice versa. The specification also provides no description on what orthologs of the cytosine deaminases would be capable of the claimed function of the claims.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the specific sequences listed within the SEQ ID NOs 12-22, listed in the claims, as well as specific substitutions of a charged amino acid with a non-polar amino acid and not the broad variants currently claimed. The results are not necessarily predictive of a cytidine or adenosine deaminase variant that is capable of functioning for the specific functions. Thus, it is impossible for one to extrapolate from the few examples described herein those variants that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of variants of cytosine and adenine deaminases. Mok et al (Nat Commun 13, 4038 (2022); Supplemental Information Pages 1/30-30/30) teaches to obtain nontoxic, full-length DddAtox variants useful for base editing, they took two different approaches: structure-based, site-directed mutagenesis (Fig. 1) and random mutagenesis (Page 2, Column 1). the E1347A variant combined with the quintuple AAAAA mutation, however, failed to induce base editing (Page 2, Column 1). Mok teaches subcloning synthetic DNA segments encoding DddAtox variants, in which positively charged amino-acid residues were replaced with alanine (Fig. 1a), in an expression vector, reasoning that these variants would bind to negatively charged dsDNA with reduced affinity, potentially avoiding toxicity, however most of the Ala-substituted variants failed to produce E. coli transformants (Page 2, Column 2).
Guo et al (Mol Cell. 2023 May 18;83(10):1710-1724.e7) teaches that they subjected the protein sequences of DddAtox (1,264–1,427 amino acids [aa]) from Burkholderia cenocepacia to BLAST alignment to search for orthologs from the top 100 hits according to the following criteria: (1) 30%– 99.9% sequence similarity with DddAtox; ( 2) the presence of an SCP1.201-like deaminase domain; (3) unbiased selection of one DddAtox ortholog from a single subspecies; and (4) the presence of a conserved catalytic activation site ‘‘E’’ (E1347 for DddAtox) (Page 1712, Column 1 bridging Column 2). Gou teaches ultimately they obtained 13 candidates, with 10 conserved amino acids within the 1,343–1,395 aa region (including E1347) and high peptide similarity with DddAtox ranging from 36.5% to 90.6% (1,264–1,427 aa); however, considering the potential toxicity of these DddAtox orthologs, they were split into two parts referring to the G1333 or G1397 split site for DddAtox18; thus, 6 candidate deaminases possessing conserved amino acids at the G1333, G1397, and/or A1398 sites were further selected for the nuclear DNA editing test (Page 1712, Column 2). Gou teaches that there are a finite number of orthologs with similarity of sequence and function that would be capable of functioning as a cytosine deaminase for successful base editing with the fusion protein.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 97-115.
Response to Arguments - Claim Rejections - 35 USC § 112
The previous rejection of claims 55-57, 59-79 and 81-96 under 35 U.S.C. 112(a) has been withdrawn in view of Applicant’s cancelation of the claims filed on 06/02/2026. The rejection has been re-written to address the new claims filed on 06/02/2026.
In the interest of compact prosecution, Applicant’s arguments have been fully considered but have not been found persuasive. Applicant argues the specification provides representative examples of split cytosine deaminase and adenine deaminase, respectively. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the specific split cytosine deaminase and adenine deaminase, respectively) 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).
The previous rejection of claims 77, 86-88 and 96 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s cancelation of the claims filed on 06/02/2026.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 97-104, 106-113 and 115 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Liu et al (WO 2021/155065 A1; Cited in a prior Office Action) as evidenced by Liu et al (US 2018/0073012 A1; Cited in a prior Office Action). This is a NEW Rejection necessitated by the amendment to the claims filed on 06/02/2026.
Regarding claims 97, 98 and 100, Liu teaches engineered split-DddA halves that are
non-toxic and inactive until brought together on target DNA by adjacently bound
programmable DNA-binding proteins (Page 1, Abstract). Liu teaches the sequence of the DddAtox as SEQ ID NO: 338 which is 100% identical to instant SEQ ID NO: 1 (See Appendix I). Liu teaches DddAtox (G1333 DddAtox-N and G1333 DddAtox-C) halves split with the split at G44 for the N-terminal and P45 for the C-terminal and fused to a TALE nuclease ([0090, 0343 and 0344] and Page 605, Fig 26A). Liu teaches the fusion protein comprising the first split and the fusion protein comprising the second split further comprises an adenine deaminase (TadA) derived from E. coli [0159, 0532 and 0709].
Regarding claim 99, Liu teaches the structure of the fusion protein as [mitoZFP]-[DddA half A] and [mitoZFP]-[DddA half B] [0031-0034]. Liu teaches the sequence of the DddAtox as SEQ ID NO: 338 which is 100% identical to instant SEQ ID NO: 1 (See Appendix I). Liu teaches a pair of mtDNA base editors each comprising a mitoZFP (mitoZFP A and mitoZFP B) fused to an inactive fragment of DddA (DddA halfA and DddA halfB) [0063].
Regarding claim 101, Liu teaches the fusion protein comprising the first split and the fusion protein comprising the second split further comprises an adenine deaminase (TadA) derived from E. coli [0159, 0532 and 0709]. Liu teaches the sequence for the ecTadA used was taken from U.S. Patent 2018/0073012 A1. Liu et al (US 2018/0073012 A1) is only cited to show that the ecTadA used is a tRNA-specific adenosine deaminase [0002, 0112 and 0377].
Regarding claims 102 and 103, Liu teaches engineered split-DddA halves that are non-toxic and inactive until brought together on target DNA by adjacently bound programmable DNA-binding proteins (Page 1, Abstract). Liu teaches DddAtox (G1397 DddAtox-N and G1397 DddAtox-C) halves split with the split at G108 for the N-terminal and A109 for the C-terminal and fused to a TALE nuclease ([0089, 0345 and 0346] and Page 605, Fig 26A).
Regarding claims 104 and 106, the claims provide an intended use but do not further modify the structure of the base editing composition. See MPEP 2111.02 (II).
Liu teaches engineered split-DddA halves that are non-toxic and inactive until brought together on target DNA by adjacently bound programmable DNA-binding proteins (Page 1, Abstract). Liu teaches the composition is for nuclear DNA base editing and comprises a nuclear localization signal (NLS) peptide [0099]. Liu teaches mitochondrial DNA base editing and further comprising a mitochondrial targeting signal (MTS) [0098].
Regarding claims 107, 108 and 110, Liu teaches engineered split-DddA halves that are
non-toxic and inactive until brought together on target DNA by adjacently bound
programmable DNA-binding proteins (Page 1, Abstract). Liu teaches the sequence of the DddAtox as SEQ ID NO: 338 which is 100% identical to instant SEQ ID NO: 1 (See Appendix I). Liu teaches DddAtox (G1333 DddAtox-N and G1333 DddAtox-C) halves split with the split at G44 for the N-terminal and P45 for the C-terminal and fused to a TALE nuclease ([0090, 0343 and 0344] and Page 605, Fig 26A). Liu teaches the fusion protein comprising the first split and the fusion protein comprising the second split further comprises an adenine deaminase (TadA) derived from E. coli [0159, 0532 and 0709].
Regarding claim 109, Liu teaches the structure of the fusion protein as [mitoZFP]-[DddA half A] and [mitoZFP]-[DddA half B] [0031-0034]. Liu teaches the sequence of the DddAtox as SEQ ID NO: 338 which is 100% identical to instant SEQ ID NO: 1 (See Appendix I). Liu teaches a pair of mtDNA base editors each comprising a mitoZFP (mitoZFP A and mitoZFP B) fused to an inactive fragment of DddA (DddA halfA and DddA halfB) [0063].
Regarding claim 111, Liu teaches the fusion protein comprising the first split and the fusion protein comprising the second split further comprises an adenine deaminase (TadA) derived from E. coli [0159, 0532 and 0709]. Liu teaches the sequence for the ecTadA used was taken from U.S. Patent 2018/0073012 A1. Liu et al (US 2018/0073012 A1) is only cited to show that the ecTadA used is a tRNA-specific adenosine deaminase [0002, 0112 and 0377].
Regarding claims 112, 113 and 115, the claims provide an intended use but do not further modify the structure of the base editing composition. See MPEP 2111.02 (II).
Liu teaches engineered split-DddA halves that are non-toxic and inactive until brought together on target DNA by adjacently bound programmable DNA-binding proteins (Page 1, Abstract). Liu teaches the composition is for nuclear DNA base editing and comprises a nuclear localization signal (NLS) peptide [0099]. Liu teaches mitochondrial DNA base editing and further comprising a mitochondrial targeting signal (MTS) [0098].
Response to Arguments - Claim Rejections - 35 USC § 102
The previous rejection of claims 55, 57, 58, 60, 62-73, 76, 77 and 86-88 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Liu et al (WO 2021/155065 A1) as evidenced by Liu et al (US 2018/0073012 A1) has been withdrawn in view of Applicant’s cancelation to the claims filed on 06/02/2026. The rejection has been re-written to address the new claims filed on 06/02/2026.
The previous rejection of claims 55, 57, 58, 62, 64, 65 and 72-76 under 35 U.S.C. 102(a)(1) as being unpatentable over Baek et al (Plants 7, 899–905 (July 1, 2021); Supplemental Information Pages 1/23-23/23) has been withdrawn in view of Applicant’s cancelation to the claims filed on 06/02/2026. The rejection has been re-written to address the new claims filed on 06/02/2026.
In the interest of compact prosecution, Applicant’s arguments have been fully considered but have not been found persuasive. Applicant argues that Liu does not disclose any composition in which a cytosine deaminase component is combined with an adenine deaminase in a single fusion protein or composition for base editing. Applicant continues to argue that Liu does not disclose any composition capable of achieving adenine (A)-to-guanine (G) base editing in organellar DNA. Applicant argues that either alone or in combination, Liu and Baek do not teach the limitation of the claims or have the motivation to combine a cytosine deaminase component with an adenine deaminase in a single composition, nor to develop a TadA-based A-to-G system for organellar DNA.
However, Liu teaches the fusion protein of DddAtox, TadA and CDD, which would comprise the DddAtox, adenine deaminase (TadA) and cytosine deaminase domain such as APOBEC [0709]. Therefore, Liu does teach a cytosine deaminase component is combined with an adenine deaminase in a single fusion protein which would be a composition for base editing.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a composition capable of achieving adenine (A)-to-guanine (G) base editing in organellar DNA) 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).
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.
Claims 105 and 114 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2021/155065 A1; Cited in a prior Office Action) as evidenced by Liu et al (US 2018/0073012 A1; Cited in a prior Office Action) in view of Baek et al (Plants 7, 899–905 (July 1, 2021); Supplemental Information Pages 1/23-23/23; Cited in a prior Office Action). This is a NEW Rejection necessitated by the amendment filed on 06/02/2026.
The teachings of Liu are described above and applied as before.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP § 215 and 216.
Regarding claim 105 and 114, the claims provide an intended use but do not further modify the structure of the base editing composition. See MPEP 2111.02 (II).
Liu teaches the use of the invention within cells originating from organisms such as animals, plants and fungi [0594].
Liu does not teach wherein the composition is for chloroplast DNA base editing and optionally further comprises a chloroplast transit peptide (CTP).
Baek teaches plasmids encode fusion proteins composed of a chloroplast transit peptide (CTP) or a mitochondrial targeting sequence (MTS), the TALE N- or C-terminal domains, split-DddAtox halves (G1333N, G1333C, G1397N and G1397C) and UGI, which are codon-optimized for expression in dicot plants, under the control of the parsley ubiquitin (PcUbi) promoter and pea3A terminator (Page 899, Column 2). Baek teaches DddAtox (G1397 DddAtox-N and G1397 DddAtox-C) halves split with the split at G108 for the N-terminal and A109 for the C-terminal and fused to a TALE nuclease (Supplemental Information Page 20). Baek teaches DddAtox (G1333 DddAtox-N and G1333 DddAtox-C) halves split with the split at G44 for the N-terminal and P45 for the C-terminal and fused to a TALE nuclease (Supplemental Information Page 20). Baek teaches a Golden Gate assembly system to construct chloroplast-targeting DdCBE (cp-DdCBE) plasmids or mitochondrial-targeting DdCBE (mt-DdCBE) plasmids (Page 899, Column 2). Baek teaches plasmids encode fusion proteins composed of a chloroplast transit peptide (CTP), the TALE N- or C-terminal domains, split-DddAtox halves (G1333N, G1333C, G1397N and G1397C) and UGI, which are codon-optimized for expression in dicot plants, under the control of the parsley ubiquitin (PcUbi) promoter and pea3A terminator (Page 899, Column 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the MTS of Liu to include the CTP for base editing within chloroplast DNA as taught by Baek because Liu teaches it is within the ordinary skill in the art to use DddAtox (G1333 DddAtox-N and G1333 DddAtox-C) halves split with the split at G44 for the N-terminal and P45 for the C-terminal and fused to a TALE nuclease wherein the second split further comprises an adenine deaminase (TadA) derived from E. coli and Baek teaches plasmids encode fusion proteins composed of a chloroplast transit peptide (CTP), the TALE N- or C-terminal domains, split-DddAtox halves (G1333N, G1333C, G1397N and G1397C) and UGI, which are codon-optimized for expression in dicot plants, under the control of the parsley ubiquitin (PcUbi) promoter and pea3A terminator for chloroplast DNA base editing.
One would have been motivated to make such a modification in order to receive the expected benefit of chloroplast DNA base editing in plant cells as taught by Baek.
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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