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 .
Priority
This application is a 371 of PCT/JP2021/014096 filed on 03/31/2021, and claim the benefit of Foreign Applications JAPAN 2020-065065 filed 03/31/2020. A certified copy of JP 2020-065065 was filed of the record on 09/28/2022. No English translation of JP 2020-065065 has been provided. Accordingly, the priority of amended claim set filed on 09/28/2022 is determined to be 03/31/2021, the filing date of PCT/JP2021/014096.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Election/Restriction
Applicant’s election without traverse of Group I, claims 1, 5 and 6, in the reply filed on 07/14/2025 is acknowledged. Claims 2-4 and 7-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Applicant’s election without traverse of SEQ ID No: 1 (136 amino acid residues) as the elected species, in the reply filed on 07/14/2025 is acknowledged. Claims 5 and 6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species (non-elected SEQ ID NO: 3 and SEQ ID NO: 90), there being no allowable generic or linking claim. Newly added SEQ ID NO: 68, 69, 70 recited in amended claim 1 filed on 01/28/2026 are directed non-elected species.
Status of claims
Applicant’s response field on 01/28/2026 have been entered. Claim 1 is amended. Claims 13-16 are newly added. Claim 16, further broadening the scope of claim 1, is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species (non-elected SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO: 41, SEQ ID NO: 54, and EQ ID NO: 72, 74, 76, 77, 78, 80, 81, 82, 84, 86, 87, 88, 89, and 90), there being no allowable generic or linking claim.
Claims 1-16 are pending. Claims 2-12 and 16 are withdraw. Claim 1 and 13-15 are currently under examination, and SEQ ID NO:1 (elected species) is examined to the extent of limitations recited in amended claim 1 a) filed on 01/28/2026.
Summary of this Final Office Action
Previous objection of claim 1 because of the following informalities: claim 1 recites “a. ---, b. ---, c. ---and bc. ---”, is withdrawn in view of claim amendments filed on 01/28/2026.
Previous rejection of claim 1 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, is withdrawn in view of claim amendments filed on 01/28/2026.
Previous rejection of claim 1 under 35 U.S.C. 103 as being unpatentable over Oldenkott et al. (2019) (Oldenkott et al., Plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing in Escherichia coli, Commun Biol. 2019 Mar 1:2:85. doi: 10.1038/s42003-019-0328-3. eCollection 2019) in view of Nakamura et al. (2014/0335521 A1, Application # 14/352,697, published on 11/13/2014), is withdrawn in view of claim amendments filed on 01/28/2026.
Previous rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 and 11 of Nakamura et al. (U.S. Patent No. 10,340,028, Date of Patent July 2, 2019, Application # 15/962,127) to in view of Oldenkott et al. (2019) (Oldenkott et al., Plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing in Escherichia coli, Commun Biol. 2019 Mar 1:2:85. doi: 10.1038/s42003-019-0328-3. eCollection 2019), and Nakamura et al. (2014/0335521 A1, US application # 14/352,697, published on 11/13/2014), is withdrawn in view of claim amendments filed on 01/28/2026.
A new ground of rejection of claim 1 under 35 U.S.C. 103 is documented below in this Final Office Action. This rejection is necessitated by claim amendments filed on 01/28/2026,
A new ground of rejection of claim 1 on the ground of nonstatutory double patenting is documented below in this Final Office Action. This rejection is necessitated by claim amendments filed on 01/28/2026,
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 1 and 13-15 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 matter rejection.
Amended claim 1 filed on 01/28/2026 is directed to “A method for editing a target RNA, the method comprising applying to the target RNA an artificial DYW protein containing a DYW domain consisting of any one of the polypeptides a), b) c), and bc) mentioned below:
a) a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 1, and having a C-to-U editing activity, b) a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 2, and having a C-to-U editing activity, c) a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 3, and having a U-to-C editing activity, or a polypeptide of SEO ID NO: 68 69 or 70, and bc) a polypeptide having a sequence identity of at least 4-080% to the sequence of SEQ ID NO: 90, and having a U-to-C editing activity; allowing the artificial DYW protein to bind to the target RNA and editing the target RNA by the artificial DYW protein.
In the remarks filed on 01/28/2026 Applicants asserted that “Support for the amendments can be found in paragraphs 0081 and 0133 of the present specification as originally filed. See also Tables 4-1 to 4-3 which discloses specific exemplary sequences having sequence identity to the corresponding sequence, which falls within the claimed respective ranges. See also paragraphs 0155-0157 of the present specification”.
However, it is unclear what the statement “Support for the amendments can be found in paragraphs 0081 and 0133 of the present specification as originally filed” actually means. This is because Applicants did not explicitly indicate which disclosure in which paragraph is relied on to support the amended limitation “at least 80% to the sequence of SEQ ID NO: 1”. The examiner cannot locate such a disclosure from disclosures in paragraphs 0081 and 0133, and a text search of specification filed on 09/28/2022 cannot locate a disclosure supporting limitation “at least 80% to the sequence of SEQ ID NO: 1” either.
For the clarity of record, Tables 4-1 to 4-3 of instant specification field on 09/28/2022 are recreated below. It is unclear how Tables 4-1 to 4-3 and paragraphs 0155-0157 support the amended limitation “at least 80% to the sequence of SEQ ID NO: 1” as asserted by Applicants.
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Newly added claims 13-15 filed on 01/28/2026 depend from claim 1.
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.
Claims 1 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Oldenkott et al. (2019) (Oldenkott et al., Plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing in Escherichia coli, Commun Biol. 2019 Mar 1:2:85. doi: 10.1038/s42003-019-0328-3. eCollection 2019) in view of Nakamura et al. (US 2014/0335521 A1, Application # 14/352,697, published on 11/13/2014), and Coffin (US 2019/024198 A1, Application # 15/732,766, published on 08/15/2019).
Claim interpretations: The limitation “a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 1” recited in claim 1 encompasses any fragment of the sequence of SEQ ID NO: 1 that is at least 80% identical to the sequence of SEQ ID NO: 1.
Regarding claims 1 and 13-15, Oldenkott et al. (2019) teaches that “RNA editing converting cytidines into uridines is a hallmark of gene expression in land plant chloroplasts and mitochondria. Pentatricopeptide repeat (PPR) proteins have a key role in target recognition, but the functional editosome in the plant organelles has remained elusive. Here we show that individual Physcomitrella patens DYW-type PPR proteins alone can perform efficient C-to-U editing in Escherichia coli reproducing the moss mitochondrial editing. Single amino acid exchanges in the DYW domain abolish RNA editing, confirming it as the functional cytidine deaminase. The modification of RNA targets and the identification of numerous off-targets in the E. coli transcriptome reveal nucleotide identities critical for RNA recognition and cytidine conversion. The straightforward amenability of the new E. coli setup will accelerate future studies on RNA target recognition through PPRs, on the C-to-U editing deamination machinery and towards future establishment of transcript editing in other genetic systems.” (See Abstract). It is noted that Physcomitrella patens a moss encompassing a eukaryotic cell recited in instant claim 13, a bryophyte used as a model organism for studies on plant evolution, development, and physiology.
Oldenkott et al. (2019) further teaches that “The bacterial system allows for straightforward identification of the key determinants for efficient C-to-U editing both on the side of the editing protein and on the RNA target side. PPR65 has been identified as the editing factor addressing editing event ccmFCeU103PS in P. patens mitochondria (for nomenclature see Fig. 1) and binding to its target was previously demonstrated in vitro by RNA electromobility shift assays after successful expression in E. coli. We adapted an expression system (see Methods), allowing insertion of target sequences behind the editing factor coding sequences on the same transcript (Fig. 1a). Indeed, isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced E. coli cultures edited the target cytidine very efficiently from 70 up to 100% (Fig. 1b). Deleting the C terminus of PPR65, essentially reducing it to its array of 15 PLS-type PPRs, abolished C-to-U conversion completely (Fig. 1b). (See bridging paragraph, pages 2-3).
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Fig. 1 Strategy for establishing a plant C-to-U RNA editing setup in Escherichia coli, shown for P. patens pentatricopeptide repeat (PPR) protein PPR65 and its target editing site ccmFCeU103PS. a The PPR65 coding sequence is inserted into the pETG_41K vector system resulting in the fusion to a His6-tagged maltose binding protein (MBP, RBS: ribosome binding site). The editing target sequence is cloned downstream. Expression is driven by a T7 promoter inducible by isopropyl β-D-1-thiogalactopyranoside (IPTG). Editing site is labeled with target gene name (ccmFC encoding subunit FC of the cytochrome c maturation machinery) followed by eU, transcript position, and resulting amino acid change. b Editing of ccmFC103PS by PPR65 relies on its C-terminal domain in E. coli. Shown are protein expression and sequencing electropherograms revealing editing frequencies for two independent E. coli cultures with PPR65 and C terminally truncated PPR65, respectively, and non-induced samples as negative controls. Bacterial lysates on a denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel correspond to ca. 4.5 × 107 cells of a 20-h culture after IPTG induction (n.i. = non-induced, PPR65trunc = C terminally truncated)
Oldenkott et al. (2019) does not explicitly teach the limitation “a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 1” recited in claim 1.
SEQ ID NO: 1 (136 amino acid residues) of instant application
EPGCSWIEVNNKVHEFVAGDKSHPQTKEIYAELERLSKQMKEAGYVPDTKFVLHDVEEEEKEQLLCYHSEKLAIA FGLISTPPGTPLRIIKNLRVCGDCHTATKFISKIVGREIVVRDANRFHHFKDGVCSCGDYW
(i) Nakamura et al. (US 2014/0335521) teaches “A method for designing a protein capable of binding in an RNA base selective manner or RNA base sequence specific manner is provided. The protein of the present invention is a protein containing one or more of PPR motifs (preferably 2 to 14 PPR motifs) each consisting of a polypeptide of 30- to 38-amino acid length represented by the formula 1 (wherein Helix A is a moiety of 12-amino acid length capable of forming an a-helix structure, and is represented by the formula 2, wherein, in the formula 2, A1 to A12 independently represent an amino acid; X does not exist, or is a moiety of 1- to 9-amino acid length; Helix Bis a moiety of 11- to 13-amino acid length capable of forming an a-helix structure; and L is a moiety of 2- to 7-amino acid length represented by the formula 3, wherein, in the formula 3, the amino acids are numbered "i" (-1), "ii" (-2), and so on from the C-terminus side, provided that Liii to Lvii,, may not exist), and combination of three amino acids A1 , A4 and Liii or combination of two amino acids A4 , and Lii is a combination corresponding to a target RNA base or base sequence. (See Abstract).
SEQ ID NO: 1 of instant application is 77.6% identical to SEQ ID NO: 30 taught by Nakamura et al. (US 2014/0335521). The sequence alignment SEQ ID NO: 1 of instant application (Qy) and SEQ ID NO: 30 taught by Nakamura et al. (Db) is provided below.
RESULT 20
US-14-352-697-30
(NOTE: this sequence has 6 duplicates in the database searched.
See complete list at the end of this report)
Sequence 30, US/14352697
Publication No. US20140335521A1
GENERAL INFORMATION
APPLICANT: Kyushu University
TITLE OF INVENTION: A method for designing RNA binding protein using PPR motif and a use thereof.
FILE REFERENCE: FA5002-12117PCT
CURRENT APPLICATION NUMBER: US/14/352,697
CURRENT FILING DATE: 2014-04-18
PRIOR APPLICATION NUMBER: JP2011-231346
PRIOR FILING DATE: 2011-10-21
NUMBER OF SEQ ID NOS: 591
SEQ ID NO 30
LENGTH: 804
TYPE: PRT
ORGANISM: Physcomitrella patens
Query Match 77.6%; Score 574; Length 804;
Best Local Similarity 74.3%;
Matches 101; Conservative 18; Mismatches 17; Indels 0; Gaps 0;
Qy 1 EPGCSWIEVNNKVHEFVAGDKSHPQTKEIYAELERLSKQMKEAGYVPDTKFVLHDVEEEE 60
||| ||||: :|| ||| |:|||:|:||||||| | |||| ||||||:||:||:::|
Db 669 EPGRSWIEIAGEVHSFVARDQSHPRTQEIYAELETLKKQMKSLGYVPDTRFVMHDLDDEG 728
Qy 61 KEQLLCYHSEKLAIA FGLISTPPGTPLRIIKNLRVCGDCHTATKFISKIVGREIVVRDAN 120
||: :|:||||||||:||||||||||:|| |||||| |||||||||||| |||: |||:
Db 729 KERAVCHHSEKLAIA YGLISTPPGTPIRISKNLRVCTDCHTATKFISKITKREIIARDAH 788
Qy 121 RFHHFKDGVCSCGDYW 136
||||||:| |||||||
Db 789 RFHHFKNGECSCGDYW 804
(ii) Coffin (US 2019/0249198) teaches that “Transgenic seed for crops with enhanced agronomic traits are provided by trait-improving recombinant DNA in the nucleus of cells of the seed where plants grown from such transgenic seed exhibit one or more enhanced traits as
compared to a control plant. Of particular interest are transgenic plants that have increased yield. The present invention also provides recombinant DNA molecules for expression of a protein, and recombinant DNA molecules for suppression of a protein” (See Abstract).
Coffin (US 2019/0249198) further teaches that “Recombinant DNA used in this invention can also be used to provide plants having improved growth and development, and ultimately increased yield, as the result of modified expression of plant growth regulators or modification of cell cycle or photosynthesis pathways” (See [0038] of Coffin); “In other aspects of the invention, sufficient expression in plant seed tissues is desired to affect improvements in seed composition. Exemplary promoters for use for seed composition modification include promoters from seed genes such as napin (U.S. Pat. No. 5,420,034), maize L3 oleosin (U.S. Pat. No. 6,433,252), zein Z27 (Russell e al. (1997) Transgenic Res. 6(2):157-166), globulin 1 (Belanger et al (1991) Genetics 129:863-872), glutelin 1 (Russell (1997) supra), and peroxiredoxin antioxidant (Perl) (Stacyet al. (1996) Plant Mal Biol. 31(6):1205-1216) (See [0049] of Coffin); and “Arabidopsis thaliana is used a model for genetics and metabolism in plants. A two-step screening process was employed which included two passes of trait characterization to ensure that the trait modification was dependent on expression of the recombinant DNA, but not due to the chromosomal location of the integration of the transgene” (See [0066] of Coffin).
Furthermore, SEQ ID NO: 1 of instant application is 80.3% identical to SEQ ID NO: 273336 taught by Coffin (US 2019/024198). The sequence alignment SEQ ID NO: 1 of instant application (Qy) and SEQ ID NO: 27336 taught by Coffin (Db) is provided below.
It is noted that Picea sitchensis, taught by Coffin (2019), commonly known as the Sitka spruce, is a large, coniferous, evergreen tree.
RESULT 1
US-15-732-766-27336
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 27336, US/15732766
Patent No. 10696975
GENERAL INFORMATION
APPLICANT: Marie Coffin
TITLE OF INVENTION: Genes and Uses for Plant Improvement
FILE REFERENCE: 38-21(54976)A-PCT
CURRENT APPLICATION NUMBER: US/15/732,766
CURRENT FILING DATE: 2019-04-15
NUMBER OF SEQ ID NOS: 94734
SEQ ID NO 27336
LENGTH: 370
TYPE: PRT
ORGANISM: Picea sitchensis
Query Match 80.3%; Score 594; Length 370;
Best Local Similarity 76.5%;
Matches 104; Conservative 15; Mismatches 17; Indels 0; Gaps 0;
Qy 1 EPGCSWIEVNNKVHEFVAGDKSHPQTKEIYAELERLSKQMKEAGYVPDTKFVLHDVEEEE 60
||||||||| |||| |: || |||| :||| || |: ||| |||:|:| |||||||||:
Db 235 EPGCSWIEVQNKVHPFIVGDSSHPQIEEIYETLETLTLQMKAAGYIPNTNFVLHDVEEEQ 294
Qy 61 KEQLLCYHSEKLAIA FGLISTPPGTPLRIIKNLRVCGDCHTATKFISKIVGREIVVRDAN 120
|| :| :||||||||||:||||||| :|::|||||||||||||||||:|| ||||:|| :
Db 295 KEWILGHHSEKLAIA FGIISTPPGTTIRVVKNLRVCGDCHTATKFISRIVSREIVLRDTH 354
Qy 121 RFHHFKDGVCSCGDYW 136
|||||||| |||||||
Db 355 RFHHFKDGQCSCGDYW 370
Regarding claim 13, in addition to Physcomitrella patens taught by Oldenkott et al. (2019), Nakamura et al. (2014) teaches that “Many kinds of PPR proteins exist in plants, and in the case of Arabidopsis thaliana, about 500 kinds of proteins and about 5000 kinds of the motifs can be found. Also in many land plants, such as rice plant, poplar, and selaginella, PPR motifs and PPR proteins of various amino acid sequences exist. It is known that some PPR proteins are important factors for obtaining Fl seeds for hybrid vigor as a fertility restoration factor that works for pollen (male gamete) formation. As an action analogous to the fertility restoration, it has been clarified that some PPR proteins work for speciation. It has also been clarified that most of PPR proteins act on RNA in mitochondria or chloroplasts” (See [0083]; and “For animals, it is known that anomaly of the PPR protein identified as LRPPRC causes Leigh syndrome French Canadian type (LSFC, Leigh's syndrome, subacute necrotizing encephalomyelopathy) (See [0084]).
It would have been prima facia obvious for a skilled artisan to combine the teachings of Nakamura et al. into the teachings of Oldenkott et al. to reach the method recited in claim 1 of instant application with reasonable expectation of success because both Oldenkott et al. and Nakamura et al. are directed to structural and functional analyses of DYW-type PPR proteins capable of RNA editing converting cytidines into uridines in the context of regulating gene expression. Applying the teachings of Oldenkott et al. (2019) and Nakamura et al. (2014) regarding RNA editing into the teachings Coffin (2019) regarding modifying gene expression of interest that enhances agronomic traits for increased yield of crops would have been prima facia obvious for a skilled artisan.
A skilled artisan would have been motivated to incorporate the teachings by Nakamura et al. into the teachings of Oldenkott et al. because Nakamura et al. specific teaches a method for designing a DYW domain containing PPR protein capable of binding in an RNA base selective manner or RNA base sequence specific manner (See for instance [0047] and Fig. 9 of Nakamura et al.) that clearly complement the teachings by Oldenkott et al. regarding plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing. Furthermore, the sequences taught by Coffin (2014) in Picea sitchensis, a large, coniferous, evergreen tree, clearly meet the requirement the limitation “a polypeptide a sequence identity of at least 80% to the sequence of SEQ ID NO: 1” recited in instant claim1.
Applicant’s arguments
Claim 1 has been amended to recite, among other features, "a polypeptide having a
sequence identity of at least 80% to the sequence of SEQ ID NO: 1, and having a C-to-U editing
activity, or a polypeptide of SEQ ID NO: 41." It is respectfully submitted that the rejection is
made moot by the amendments and should be withdrawn since a prima facie case of obviousness
is not established by the currently cited references as they fail to disclose the currently claimed
subject matter. The other sequences species have also been amended in a similar manner and can be rejoined.
Further, Nakamura discloses the presence of a DYW domain linked to a PPR protein (see Figs. 4, 9, and 13; Example 2). However, Example 2 also indicates that the DYW domain is frequently absent. Moreover, Nakamura provides no disclosure whatsoever regarding structural characteristics of the DYW domain such as a polypeptide or specific ammo acid sequence
constituting the domain. The Examiner is respectfully reminded that it is "impermissible, [],
simply to engage in a hindsight reconstruction of the claimed invention, using the applicant's
structure as a template and selecting elements from the references to fill the gaps." In re Gorman,
983 F.2d 982, 987 (Fed. Cir. 1991).
Absent access to the disclosure in the present specification, no one would have correlated
SEQ ID NO: 30 of Nakamura with a DYW domain consisting of the claimed polypeptides having C-to-U or U-to-C editing activity. Accordingly, Nakamura cannot be relied upon to provide any technical teaching or guidance concerning the sequence of a functionally active DYW domain. It is respectfully submitted that there is no reasonable expectation of success to combine Oldenkott and Nakamura to arrive at the claimed invention.
Response to Applicant’s arguments
Applicant’s arguments have been thoroughly reviewed and found not persuasive in the context of new grounds of rejection of claims 1 and 13-15 under 35 U.S.C. 103 as being unpatentable over Oldenkott et al. (2019) in view of Nakamura et al. (US 2014/0335521) and Coffin (US 2019/024198) documented in this Final Office Action. In this regard, it is worth noting that primary reference Oldenkott et al. (2019) explicitly provides disclosure in Fig. 2 and Fig. 3. regarding structural characteristics of the DYW domain such as a polypeptide or specific ammo acid sequence constituting the domain.
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Fig. 2 DYW-type pentatricopeptide repeat (PPR) protein PPR65 and its corresponding RNA editing site ccmFCeU103PS tested for target nucleotide (a) and amino acid mutations (b) in the new E. coli setup. a Labels of PLS-type PPRs use backward numbering (top numbers) with S-1 juxtaposed to nucleotide −4 (bottom numbers) upstream of the editing site (red) and indicate the respective amino acid identities in PPR positions 5 and L (last). The terminal P2L2S2 PPR triplet is underlined. Target nucleotide color shading is according to the PPR-RNA code for P- and S-type PPRs (gray, T/S +N: A, T/S + D: G, N + N: C/U, N + S: C > U, N+ D: U > C) with green for perfect matches, blue for pyrimidine transitions, yellow for purine transitions, and pink for mismatches. Exceptionally, L-type PPR L-5TD (dark gray) would also match the G in position −8 of the native target. b Amino acid identities 5 or L of selected PPRs and conserved residues of the assumed Zn2+-binding cytidine deaminase signature and the carboxy-terminal DFW motif in the DYW domain (shown in blue) were changed as indicated. Introduced PPR mutations (left part, bold) were attempted to be compensated with corresponding mutations A-to-U and G-to-A in positions −7 and −6 in the target, respectively. RNA editing efficiencies are given as the mean ± s.d. of at least three biological replicates (independent primary E. coli clones) when at least some RNA editing activity was initially detected. The absence of RNA editing was confirmed with at least an additional clone. Primary data are listed in Supplementary Data 1.
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Fig. 3 Dual-target editing factor pentatricopeptide repeat protein PPR56 expressed in the E. coli system with efficient editing of nad4eU272SL and partial editing of nad3eU230SL site. Designation of PPRs, numbering of positions, shading, and the scoring of editing efficiencies is as in Fig. 2. Single point mutations have been introduced into each of the two targets to match the respective other sequence. For the nad4eU272SL target, a combination of all three exchanges and a variant to fully match the PPRRNA code concept have also been tested (middle). Additionally, the perfect match of an A in position −12 opposite of P-9TN was changed into G in
both targets.
One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 and 11 of Nakamura et al. (U.S. Patent No. 10,340,028, Date of Patent July 2, 2019, Application # 15/962,127) to in view of Oldenkott et al. (2019) (Oldenkott et al., Plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing in Escherichia coli, Commun Biol. 2019 Mar 1:2:85. doi: 10.1038/s42003-019-0328-3. eCollection 2019), and Nakamura et al. (2014/0335521 A1, US application # 14/352,697, published on 11/13/2014) and Coffin (US 2019/024198, Application # 15/732,766, published on 08/15/2019).
Amended claim 1 filed on 01/28/2026 is directed to “A method for editing a target RNA, the method comprising applying to the target RNA an artificial DYW protein containing a DYW domain consisting of any one of the polypeptides a), b) c), and bc) mentioned below:
a) a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 1, and having a C-to-U editing activity, b) a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 2, and having a C-to-U editing activity, c) a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 3, and having a U-to-C editing activity, or a polypeptide of SEO ID NO: 68 69 or 70, and bc) a polypeptide having a sequence identity of at least 4-080% to the sequence of SEQ ID NO: 90, and having a U-to-C editing activity; allowing the artificial DYW protein to bind to the target RNA and editing the target RNA by the artificial DYW protein.
Claim 11 of US 10,340,028 is directed to “A method for identifying a PPR protein that works as a fertility restoration factor for cytoplasmic male sterility for a target plant, wherein the PPR protein is a protein defined in claim 1, said method comprising extracting an amino acid sequence of each of three amino acids Al, A4 and Lii or two amino acids A4 and Lii from an amino acid sequence of a PPR motif of a candidate PPR protein in a plant that can be crossed with the target plant, predicting a target RNA base sequence for the candidate PPR protein based on the combination of the three amino acids Al, A4 and Lii, or two amino acids A4 and Lii.”
Claim 1 of US 10,340,028 is directed to “A method for predicting the function for the fertility restoration of a PPR protein obtained from a test plant, based on the predetermined PPR protein relating to fertility, wherein the PPR protein is a protein containing one or more
of PPR motifs each consisting of a polypeptide of 30- to 38-amino acid length represented by the formula 1: (HelixA)-X-(HelixB)-L (Formula 1) ----”
Claim 4 of US 10,340,028 is directed to “The method according to claim 1, wherein the predetermined PPR protein relating to fertility is any one selected from the group consisting of the proteins of SEQ ID NOS: 576 to 578 and 585 to 591.”
<210> SEQ ID NO 576
<211> LENGTH, 687
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 577
<211> LENGTH, 687
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 578
<211> LENGTH, 686
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 585
<211> LENGTH, 667
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 586
<211> LENGTH, 683
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 587
<211> LENGTH, 687
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 588
<211> LENGTH, 690
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 589
<211> LENGTH, 690
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 590
<211> LENGTH, 683
<212> TYPE, PRT
<213> ORGANISM, Raphanus sativus
<210> SEQ ID NO 591
<211> LENGTH, 686
<212 > TYPE, PRT
<213 > ORGANISM, Raphanus sativus
The combined teaching of Oldenkott et al. (2019), Nakamura et al. (2014/0335521), and Coffin (US 2019/024198) have been documented above in the rejection under 35 USC § 103.
In summary, Oldenkott et al. (2019) teaches that “RNA editing converting cytidines into uridines is a hallmark of gene expression in land plant chloroplasts and mitochondria. Pentatricopeptide repeat (PPR) proteins have a key role in target recognition, but the functional editosome in the plant organelles has remained elusive. Here we show that individual Physcomitrella patens DYW-type PPR proteins alone can perform efficient C-to-U editing in Escherichia coli reproducing the moss mitochondrial editing”. Nakamura et al. (2014) teaches a method for designing a DYW domain containing PPR (pentatricopeptide repeat) protein capable of binding in an RNA base selective manner or RNA base sequence specific manner (see Title and Abstract), and SEQ ID NO: 1 of instant application is 77.6% identical to SEQ ID NO: 30 taught by Nakamura et al. (2014).
<210> SEQ ID NO 30
<211> LENGTH, 804
<212> TYPE, PRT
<213> ORGANISM, Physcomitrella patens
Furthermore, SEQ ID NO: 1 of instant application is 80.3% identical to SEQ ID NO: 273336 taught by Coffin (US 2019/024198). The sequence alignment SEQ ID NO: 1 of instant application (Qy) and SEQ ID NO: 27336 taught by Coffin (Db).
RESULT 1
US-15-732-766-27336
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 27336, US/15732766
Patent No. 10696975
GENERAL INFORMATION
APPLICANT: Marie Coffin
TITLE OF INVENTION: Genes and Uses for Plant Improvement
FILE REFERENCE: 38-21(54976)A-PCT
CURRENT APPLICATION NUMBER: US/15/732,766
CURRENT FILING DATE: 2019-04-15
NUMBER OF SEQ ID NOS: 94734
SEQ ID NO 27336
LENGTH: 370
TYPE: PRT
ORGANISM: Picea sitchensis
Query Match 80.3%; Score 594; Length 370;
Best Local Similarity 76.5%;
Matches 104; Conservative 15; Mismatches 17; Indels 0; Gaps 0;
Qy 1 EPGCSWIEVNNKVHEFVAGDKSHPQTKEIYAELERLSKQMKEAGYVPDTKFVLHDVEEEE 60
||||||||| |||| |: || |||| :||| || |: ||| |||:|:| |||||||||:
Db 235 EPGCSWIEVQNKVHPFIVGDSSHPQIEEIYETLETLTLQMKAAGYIPNTNFVLHDVEEEQ 294
Qy 61 KEQLLCYHSEKLAIA FGLISTPPGTPLRIIKNLRVCGDCHTATKFISKIVGREIVVRDAN 120
|| :| :||||||||||:||||||| :|::|||||||||||||||||:|| ||||:|| :
Db 295 KEWILGHHSEKLAIA FGIISTPPGTTIRVVKNLRVCGDCHTATKFISRIVSREIVLRDTH 354
Qy 121 RFHHFKDGVCSCGDYW 136
|||||||| |||||||
Db 355 RFHHFKDGQCSCGDYW 370
Applicant’s arguments
The Examiner asserts that SEQ ID NO: 1 of the instant application is 77.6 % identical to
SEQ ID NO: 30 taught by Nakamura. As noted above, claim 1 has been amended to recite that a polypeptide having a sequence identity of at least 80% to the sequence of SEQ ID NO: 1, and
having a C-to-U editing activity, or a polypeptide of SEQ ID NO: 41. Further, as noted above,
Nakamura (2014/0335521 Al) fails to provide any technical teaching or guidance concerning the
sequence of a functionally active DYW domain as recited in claim 1.
For at least the above reasons, the DP rejection is made moot and should be withdrawn.
Response to Applicant’s arguments
Claim 1 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 and 11 of Nakamura et al. (U.S. Patent No. 10,340,028, Date of Patent July 2, 2019, Application # 15/962,127) to in view of Oldenkott et al. (2019), Nakamura et al. (2014/0335521) and Coffin (US 2019/024198).
SEQ ID NO: 1 of instant application is 80.3% identical to SEQ ID NO: 273336 taught by Coffin (US 2019/024198). The sequence alignment SEQ ID NO: 1 of instant application (Qy) and SEQ ID NO: 27336 taught by Coffin (Db).
Conclusion
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 Wu-Cheng Winston Shen whose telephone number is (571)272-3157. The examiner can normally be reached Mon.-Fri. 8:00 AM-5:00 PM.
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/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682