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 .
Status of the Claims
Claims 1-18 are pending.
Claims 1-18 are examined herein.
Claims 1-18 are rejected.
Priority
Application No. 19/113,550 filed on 03/20/2025 is a 371 of PCT/KR2023/014300 filed on 09/20/2023 and also claims priority to Korean Application No. KR10-2022-0119363 filed on 09/21/2022.
A certified copy of the PCT application has been received and is acknowledged (see FRPR doc, dated 03/20/2025).
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Korea on 09/21/2022. It is noted, however, that applicant has not filed a certified copy of the KR10-2022-0119363 application as required by 37 CFR 1.55.
Furthermore, no certified English translations of the PCT and Korean applications have been filed. 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.
Claim Interpretation
The specification recites: “ [52] The cytosine deaminase is an enzyme that removes an amino group, and enables cytosine (C) to uridine (U) conversion.
[53] The cytosine deaminase may be used. For example, there are types of cytosine deaminase, such as APOBECI (apolipoprotein B editing complex 1) and AID (activation- induced deaminase), but most DNA deaminases only work on single-stranded DNA and may not be suitable for base editing by linkage to a DNA binding protein. Specifically, the cytosine deaminase may be derived from a deaminase (DddA) acting on double-stranded DNA or an orthologue thereof. More specifically, the cytosine deaminase may be a double-stranded DNA-specific bacterial cytosine deaminase.”
Both APOBECI and DddAtox are typically known as cytidine deaminases, not cytosine deaminases as claimed and described throughout the disclosure.
For purposes of examination, “Cytosine deaminase” is broadly, reasonably interpreted to encompass any deaminase that enables C to U conversion including cytidine deaminases.
Claim Objections
Claim 8 recites:
The composition according to claim 7, wherein the linker comprises:
2a.a linker: GS;
5a.a linker: TGEIKQ (SEQ ID NO:8);
10a.a linker: SGAQGSTLDF (SEQ ID NO:9);
16a.a linker: SGSETPGTSESATPES (SEQ ID NO:10);
24 aa linker: SGTPHEVGVYTLSGTPHEVGVYTL (SEQ ID NO:45); or
32a.a linker: GSGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO:11).
The claim is objected to because there is inconsistency in how “aa linker” is written. For example, in some instances it is written “a.a linker” and in other instances it is written “aa linker”. Additionally, “a.a” or “aa” is an abbreviation that is not previously defined in the claims. It is suggested Applicant include a space after 2, 5, 10, 16, 24, and 32, and also write out “amino acid linker” in place of each recitation or “a.a linker” or “aa linker” to improve consistency and clarity.
Claim Rejections – 35 USC § 112
Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites “32a.a linker: GSGGSSGGSSGSETPGTSESATPESSGGS SGGS (SEQ ID NO: 11). However, the recited linker is 33 amino acid residues in length and SEQ ID NO: 11 is also 33 amino acids in length. It is unclear if 32 of the amino acid residues from the 33 residue sequence are required, or if the claim is meant to recite “33a.a linker” and the full length of the 33 amino acid sequence is required. For this reason, the meets and bounds of the claim are unclear.
Because a 32 aa residue sequence is commonly found in the prior art and has the sequence of “SGGSSGGSSGSETPGTSESATPESSGGSSGGS”, the first “G” in the claimed sequence is interpreted to have been included by mistake and is a typo. For purposes of examination, the claim is interpreted to require the 32 aa linker have the sequence of SGGSSGGSSGSETPGTSESATPESSGGSSGGS.
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 1, 7-8, 11-12, and 16-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li (Li, C., Zhang, R., Meng, X., Chen, S., Zong, Y., Lu, C., ... & Gao, C. (2020). Targeted, random mutagenesis of plant genes with dual cytosine and adenine base editors. Nature biotechnology, 38(7), 875-882.).
Claim 1 is drawn to a composition for editing organellar DNA in plant cells, comprising:
DNA binding protein or nucleic acid encoding the DNA binding protein;
cytosine deaminase, or first and second splits derived from cytosine deaminase, or nucleic acid encoding the same; and
adenine deaminase or nucleic acid encoding the adenine deaminase,
wherein each of the first and second splits independently binds to DNA binding protein,
and the composition simultaneously performs adenine (A)-to-guanine (G) editing and cytosine (C)-to-thymine (T) editing in plant organellar DNA.
Claim 7 is drawn to the composition according to claim 1, wherein the DNA binding protein is linked via a peptide linker comprising 2 to 40 amino acid residues.
Claim 8 is drawn to the composition according to claim 7, wherein the peptide linker comprises: 2a.a linker: GS; 5a.a linker: TGEIKQ (SEQ ID NO:8); 10a.a linker: SGAQGSTLDF (SEQ ID NO:9); 16a.a linker: SGSETPGTSESATPES (SEQ ID NO:10); 24 aa linker: SGTPHEVGVYTLSGTPHEVGVYTL (SEQ ID NO:45); or 32a.a linker: GSGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO:11).
Claim 11 is drawn to the composition according to claim 1, wherein the adenine deaminase is linked to the N-terminus or C-terminus of the DNA-binding protein or cytosine deaminase.
Claim 12 is drawn to the composition according to claim 1, wherein the adenine deaminase is deoxyadenine deaminase derived from TadA.
Claim 16 is drawn to the composition according to claim 1, wherein the composition is delivered into plant cells by means of: bombardment using a gene gun; protoplast transfection mediated by polyethylene glycol (PEG); protoplast transfection via electroporation; or protoplast injection via microinjection.
Claim 17 is drawn to the composition according to claim 1, wherein the nucleic acid is delivered into plant cells by means of: transformation using Agrobacterium tumefaciens or Agrobacterium rhizogene; viral transfection; bombardment using a gene gun; protoplast transfection mediated by polyethylene glycol (PEG);protoplast transfection via electroporation; or protoplast injection via microinjection.
Claim 18 is drawn to a method for editing organellar DNA in plant cells, comprising a step of treating plant cells with the composition according to claim 1.
Regarding claim 1, Li discloses engineering a dual-base editor for simultaneous C to T and A to G base editing comprising a cytidine deaminase (i.e. a cytosine deaminase, see claim interpretation above), an adenosine deaminase (i.e. an adenine deaminase, see claim interpretation above), and nCas9 (i.e. a DNA binding protein) (p. 875, right column, ¶2, and Fig. 1b). Regarding the limitation of “and the composition simultaneously performs adenine (A)-to-guanine (G) editing and cytosine (C)-to-thymine (T) editing in plant organellar DNA”, this does not limit the anticipated structure of the composition and is merely an intended use. Regardless, the limitation is still anticipated by Li who discloses editing OsACC gene in plant cell, which is a known gene in nuclear genome of rice (i.e. the rice nuclear genome is the plat organellar DNA) (see NLS in STEME-1 and -3 in Fig. 1, and p. 878, ¶2, and Fig. 3).
Regarding claim 7, Li discloses the DNA binding protein (nCas9) is linked to TadA via a peptide linker comprising 32 amino acid residues (Fig. 1b, see STEME-1 and STEME-3).
Regarding claim 8, Li discloses the nucleotide sequence between Cas9 and TadA encodes a 32 amino acid peptide linker that has the sequence of SGGSSGGSSGSETPGTSESATPESSGGSSGGS (supplementary sequences 1) which is identical to the 32 AA residues in the instantly claimed 32 AA linker (see 112(b)).
Regarding claim 11, Li discloses the adenine deaminase is linked to the N-terminus of the DNA-binding protein (Fig. 1b).
Regarding claim 12, Li discloses the adenosine deaminase is deoxyadenosine deaminase derived from TadA from E. coli (Fig. 1b).
Regarding claim 16, Li discloses introducing the composition into rice protoplasts via protoplast transfection mediated by polyethylene glycol (PEG) (p. 883, Methods section titled Protoplast transfection).
Regarding claim 17, Li discloses transforming bindary vectors (encoding the dual-base editors) into Agrobacterium tumefaciens, then using Agrobacteirum-mediated transformation to introduce the vectors encoding the dual-base editor into rice calli (i.e. wherein the nucleic acid is delivered into plant cells by means of transformation using Agrobacterium tumefaciens) (p. 883, Methods section titled Agrobacterium-mediated transformation of rice callus cells).
Regarding claim 18, Li discloses using Agrobacteirum-mediated transformation to introduce the vectors encoding the dual-base editor into rice calli (treating plant cells with the composition) (p. 883, Methods section titled Agrobacterium-mediated transformation of rice callus cells).
Claims 1 and 12 are separately rejected under 35 U.S.C. 102(a)(1) as being anticipated by Molla (Molla, K. A., Sretenovic, S., Bansal, K. C., & Qi, Y. (2021). Precise plant genome editing using base editors and prime editors. Nature Plants, 7(9), 1166-1187.).
Claim 1 is drawn to a composition for editing organellar DNA in plant cells, comprising:
DNA binding protein or nucleic acid encoding the DNA binding protein;
cytosine deaminase, or first and second splits derived from cytosine deaminase, or nucleic acid encoding the same; and
adenine deaminase or nucleic acid encoding the adenine deaminase,
wherein each of the first and second splits independently binds to DNA binding protein,
and the composition simultaneously performs adenine (A)-to-guanine (G) editing and cytosine (C)-to-thymine (T) editing in plant organellar DNA.
Claim 12 is drawn to the composition according to claim 1, wherein the adenine deaminase is deoxyadenine deaminase derived from TadA.
Regarding claim 1, Molla discloses a dual-base editor for simultaneous C to T and A to G base editing, comprising Cas9 (i.e. a DNA binding protein), a cytidine deaminase (i.e. a cytosine deaminase, see claim interpretation above), and an adenosine deaminase (i.e. an adenine deaminase, see claim interpretation above) (Fig. 2E).
Regarding claim 12, Molla discloses the adenosine deaminase is deoxyadenosine deaminase derived from TadA from E. coli (FIG. 2E)
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.
Claims 2-3, 6, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Molla (Molla, K. A., Sretenovic, S., Bansal, K. C., & Qi, Y. (2021). Precise plant genome editing using base editors and prime editors. Nature Plants, 7(9), 1166-1187.).
Claim 2 is drawn to the composition according to claim 1, wherein each of the first and second splits alone lacks cytosine deaminase activity.
Claim 3 is drawn to the composition according to claim 1, wherein the cytosine deaminase is derived from a double-stranded DNA deaminase (DddA) or an orthologue thereof.
Claim 6 is drawn to the composition according to claim 1, wherein the DNA binding protein is zinc-finger protein (ZF protein) or transcription activator-like effector (TALE) array.
Claim 9 is drawn to the composition according to claim 1, wherein the DNA binding protein is zinc-finger protein, and each of the first and second splits is independently linked to the N-terminus or C- terminus of the zinc-finger protein.
Claim 10 is drawn to the composition according to claim 1, wherein the DNA binding protein is TALE array, and wherein a single TALE array is linked to one terminus of the split, or first and second TALE arrays are linked to the first and second splits.
Claim 13 is drawn to the composition according to claim 1, comprising chloroplast transit peptide or nucleic acid encoding the chloroplast transit peptide.
Claim 14 is drawn to the composition according to claim 1, comprising mitochondrial targeting signal (MTS) or nucleic acid encoding the mitochondrial targeting signal.
Regarding claims 2-3, 6, and 9-10, Molla teaches the limitations of claim 1 as set forth in the previous anticipation rejection. The teachings of Molla as they are applied to claim 1 are set forth previously herein and are incorporated by reference.
However, Molla does not teach in a single embodiment:
the composition according to claim 1, wherein each of the first and second splits alone lacks cytosine deaminase activity (claim 2). That is because the anticipated embodiment (dual-base editor) disclosed by Molla is broadly drawn to any cytidine deamianse or, e.g., hAID or PmCDA1, and Molla does not explicitly teach the cytidine deaminase is split (Fig. 2e-f).
wherein the cytosine deaminase is derived from a double-stranded DNA deaminase (DddA) or an orthologue thereof (claim 3). This is because the anticipated embodiment (dual-base editor) disclosed by Molla is broadly drawn to any cytidine deaminase or, e.g., hAID or PmCDA1, and Molla does not explicitly teach the cytidine deaminase is DddA.
wherein the DNA binding protein is zinc-finger protein (ZF protein) or transcription activator-like effector (TALE) array (claim 6)
wherein the DNA binding protein is TALE array, and wherein a single TALE array is linked to one terminus of the split, or first and second TALE arrays are linked to the first and second splits (claim 10)
the composition according to claim 1, comprising chloroplast transit peptide or nucleic acid encoding the chloroplast transit peptide (claim 13)
the composition according to claim 1, comprising mitochondrial targeting signal (MTS) or nucleic acid encoding the mitochondrial targeting signal (claim 14)
Regarding claims 2-3, 6, and 10, in an alternative embodiment Molla teaches about another cytidine deaminase named DddA-derived cytosine base editor (DdCBE, also known as DddA) (p. 1175, ¶3-5, Fig. 3). Molla teaches DddA is cytotoxic, and cytotoxicity is mitigated by splitting DddA into two inactive halves (p. 1175, ¶3). Molla further teaches the inactive DddA halves are fused to left and right TALEs (i.e. the DNA binding protein is TALE, and the first and second TALE arrays are linked to the first and second splits), and DddA would be functional only once both halves reconstitute adjacently to the target DNA (p. 1175, ¶3, Fig. 3). Molla teaches the fused TALE-split DddA halves are useful to edit chloroplast and mitochondria of plants (p. 1175, ¶3-5, Fig. 3). Thus, because DddA is only functional when both halves reconstitute, Molla teaches the cytosine deaminase is derived from a double-stranded DNA deaminase (DddA), and the first and second splits of the DddA-derived cytosine base editor alone lack cytosine deaminase activity.
Regarding claim 9, Molla teaches in an alternative embodiment programable DNA-binding proteins such as zinc fingers (ZFs) and transcription-activator-like effectors (TALEs) are suitable for organellar genome editing (p. 1175, ¶2)
Regarding claims 13-14, Molla further teaches the composition of the fused TALE-split DddA halves may further comprise a mitochondrial targeting signal or a chloroplast transit peptide for mitochondria and chloroplast base editing, respectively (Fig. 3).
Molla teaches all of the limitations of the rejected claims in alternative embodiments, but does not disclose a single embodiment having all the limitations. As such, the claims are not rejected as anticipated under 35 USC §102 but are instead rejected as obvious under 35 USC §103. One of ordinary skill in the art would have been motivated to combine the limitations as taught by Molla into a single embodiment to arrive at Applicant’s claimed inventions because each limitation is explicitly taught as an alternative embodiment of the invention. It would therefore be obvious to combine the dual base editor composition disclosed by Molla with the alternative known cytidine deaminases (split DddA), the alternative known DNA binding proteins (ZFs and TALEs), and the targeting signals all taught by Molla for the same purpose that is dual base editing in plant cells, including editing the nuclear, mitochondrial, or chloroplast genomes. One having ordinary skill in the art would have a reasonable expectation of success because the compositions and method Molla teaches was functional and successful and the application to the alternative embodiments present no special technical obstacles.
Claims 4-5 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Molla as applied to claim 1-3 above, and further in view of Willis (WO-2021155065-A1, published 08/05/2021).
Claim 4 is drawn to the composition according to claim 1, wherein the first split comprises the sequence from the N-terminus to at least one residue selected from the group consisting of G33, G44, A54, N68, G82, N98, and G108 of SEQ ID NO:1.
Claim 5 is drawn to the composition according to claim 1, wherein the second split comprises the sequence from at least one residue selected from the group consisting of G34, P45, G55, N69, T83, A99, and A109 to the C-terminus residue of SEQ ID NO: 1.
Claim 15 is drawn to the composition according to claim 1, which does not comprise uracil DNA- glycosylase inhibitor (UGI).
Regarding claims 4-5 and 15, Molla teaches the limitations of claim 1-3 as set forth in the previous anticipation and obviousness rejections. The teachings of Molla as they are applied to claims 1-3 are set forth previously herein and are incorporated by reference.
However, Molla does not explicitly teach wherein the first split comprises the sequence from the N-terminus to at least one residue selected from the group consisting of G33, G44, A54, N68, G82, N98, and G108 of SEQ ID NO:1 (claim 4), nor wherein the second split comprises the sequence from at least one residue selected from the group consisting of G34, P45, G55, N69, T83, A99, and A109 to the C-terminus residue of SEQ ID NO: 1 (claim 5). This is because Molla does not explicitly identify the location of the DddA splits. Additionally, Molla provides a UGI in all Figures and examples, and therefore does not explicitly teach the composition according to claim 1, which does not comprise uracil DNA- glycosylase inhibitor (UGI).
Regarding claims 4-5, in analogous art, Willis teaches the sequence of DddA (SEQ ID NO: 338 of Willis) which has 100% sequence identity to instant SEQ ID NO: 1 (¶0338). Willis teaches the split DddA can have the sequence of G1397DddAtox-N (SEQ ID NO: 351 of Willis) which encompasses the N-terminus to G108 of SEQ ID NO:1 (¶0345). Willis also teaches the other split DddA can have the sequence of G1397DddAtox-C (SEQ ID NO: 352 of Willis) which encompasses the sequence from A109 to the C-terminus residue of SEQ ID NO: 1 (¶0346).
RESULT 1
BJS48894
(NOTE: this sequence has 24 duplicates in the database searched.
See complete list at the end of this report)
ID BJS48894 standard; protein; 138 AA.
XX
AC BJS48894;
XX
DT 16-SEP-2021 (first entry)
XX
DE DddAtox protein sequence, SEQ ID 338.
XX
KW Genome editing; alzheimers disease; antidiabetic; antiparkinsonian;
KW cancer; cardiant; cytostatic; diabetes mellitus; gastrointestinal-gen.;
KW genetic disorder; genetic-disease-gen.; growth-disorder-gen.;
KW huntingtons chorea; lysosome storage disease; metabolic disorder;
KW metabolic-gen.; mood disorder; motor neurone disease; myocardial disease;
KW nephrotropic; neurodegenerative disease; neuroprotective; nootropic;
KW parkinsons disease; prophylactic to disease; protein therapy;
KW psychiatric-gen.; recombinant protein; renal tubule disease; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2021155065-A1.
XX
CC PD 05-AUG-2021.
XX
CC PF 28-JAN-2021; 2021WO-US015580.
XX
PR 28-JAN-2020; 2020US-0967027P.
PR 12-JUN-2020; 2020US-0038741P.
XX
CC PA (BROD ) BROAD INST INC.
CC PA (UNIW ) UNIV WASHINGTON.
CC PA (HARD ) HARVARD COLLEGE.
CC PA (WILL/) WILLIS J.
XX
CC PI Willis J, Liu DR, Mok B, Mougous JD, Peterson SB, De Moraes M;
XX
DR WPI; 2021-90320P/069.
XX
CC PT Non-naturally occurring polypeptide variant, fragment used in therapeutic
CC PT kit for treatment of mitochondrial disease, diabetes, cancer, comprises
CC PT double-stranded DNA deaminase activity.
XX
CC PS Example 1; SEQ ID NO 338; 714pp; English.
XX
CC The present invention relates to a non-naturally occurring polypeptide
CC variant, useful in a therapeutic kit for treating mitochondrial disease,
CC diabetes, cancer. The polypeptide variant comprises double-stranded DNA
CC deaminase activity. The invention further relates to: (1) a non-naturally
CC occurring polypeptide fragment of double-stranded DNA deaminase; (2) a
CC base editor, which comprises the heterodimer; (3) an isolated nucleic
CC acid, which is encoding first monomer of base editor; (4) a vector, which
CC comprises isolated nucleic acid; (5) a cell, which comprises vector; (6)
CC a method for editing a target nucleotide sequence; (7) a method for
CC delivering base editor to cell; (8) a method for delivering base editor
CC to mitochondria; and (9) a therapeutic kit, which comprises the nucleic
CC acid constructs. The polypeptide is useful for treating or preventing
CC genetic disease, metabolic disease, lysosomal storage disease,
CC cardiomyopathy, renal tubular acidosis, neurodegenerative diseases,
CC Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis
CC (ALS), Huntington's Disease, mood disorders, nucleoside reverse
CC transcriptase inhibitors (NRTI) treatment, diabetes, and cancer.
XX
SQ Sequence 138 AA;
Query Match 100.0%; Score 747; Length 138;
Best Local Similarity 100.0%;
Matches 138; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSYALGPYQISAPQLPAYNGQTVGTFYYVNDAGGLESKVFSSGGPTPYPNYANAGHVEGQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GSYALGPYQISAPQLPAYNGQTVGTFYYVNDAGGLESKVFSSGGPTPYPNYANAGHVEGQ 60
Qy 61 SALFMRDNGISEGLVFHNNPEGTCGFCVNMTETLLPENAKMTVVPPEGAIPVKRGATGET 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SALFMRDNGISEGLVFHNNPEGTCGFCVNMTETLLPENAKMTVVPPEGAIPVKRGATGET 120
Qy 121 KVFTGNSNSPKSPTKGGC 138
||||||||||||||||||
Db 121 KVFTGNSNSPKSPTKGGC 138
Regarding claim 15, Willis teaches TALE-DddA constructs may be UGI-free (Fig. 8A-B and caption in ¶0072).
It would therefore have been obvious to a person of ordinary skill in the art to combine the composition as taught by Molla with the teachings of Willis to arrive at the instantly claimed method with a reasonable expectation of success because splitting the DddA at the location taught by Willis, and including or excluding a UGI from the composition as also taught by Willis, are matters of experimental design and the composition in these various embodiments may be achieved without encountering any special technical difficulties. One of ordinary skill in the art would have been motivated to combine the teachings to arrive at the instantly claimed compositions because Willis teaches the split DddA at the specific and claimed locations successfully induces base edits, and the UGI-free TALE-split halves express well in cells (0072-0073 and Figs. 8-9).
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.
Claims 1-6, 9-10, 13 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 10, 13, 17-18, 23, 31, and 40 of copending Application No. 19/162,851 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims in the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 6, 12-14 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 11, and 16-17 of copending Application No. 19/497,215 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims in the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 6, 9-11 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 13, 26-27, 29, and 31-32 of copending Application No. 19/505,063 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims in the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 9-14, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-14 of copending Application No. 19/396,735 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims in the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 9, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-14 of copending Application No. 19/448,417 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims in the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, and 9-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 97-105 and 107-114 of copending Application No. 18/025,446 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims in the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 7-8 and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the specified claims above of copending Application Nos. 19/162,851, 19/497,215, 19/505,063, 19/396,735, 19/448,417, or 18/025,446 in view of Li (Li, C., Zhang, R., Meng, X., Chen, S., Zong, Y., Lu, C., ... & Gao, C. (2020). Targeted, random mutagenesis of plant genes with dual cytosine and adenine base editors. Nature biotechnology, 38(7), 875-882.).
Application Nos. 19/162,851, 19/497,215, 19/505,063, 19/396,735, 19/448,417, or 18/025,446 each disclose the limitations of claim 1.
However, each of Application Nos. 19/162,851, 19/497,215, 19/505,063, 19/396,735, 19/448,417, or 18/025,446 do not explicitly disclose:
wherein the DNA binding protein is linked via a peptide linker comprising 2 to 40 amino acid residues (claim 7),
wherein the peptide linker comprises: 2a.a linker: GS; 5a.a linker: TGEIKQ (SEQ ID NO:8); 10a.a linker: SGAQGSTLDF (SEQ ID NO:9); 16a.a linker: SGSETPGTSESATPES (SEQ ID NO:10); 24 aa linker: SGTPHEVGVYTLSGTPHEVGVYTL (SEQ ID NO:45); or 32a.a linker: GSGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO:11) (claim 8),
wherein the composition is delivered into plant cells by means of: bombardment using a gene gun; protoplast transfection mediated by polyethylene glycol (PEG); protoplast transfection via electroporation; or protoplast injection via microinjection (claim 16),
wherein the nucleic acid is delivered into plant cells by means of: transformation using Agrobacterium tumefaciens or Agrobacterium rhizogene; viral transfection; bombardment using a gene gun; protoplast transfection mediated by polyethylene glycol (PEG);protoplast transfection via electroporation; or protoplast injection via microinjection (claim 17)
In analogous art, Li similarly teaches engineering a dual-base editor for simultaneous C to T and A to G base editing comprising a cytidine deaminase (i.e. a cytosine deaminase, see claim interpretation above), an adenosine deaminase (i.e. an adenine deaminase, see claim interpretation above), and nCas9 (i.e. a DNA binding protein) (p. 875, right column, ¶2, and Fig. 1b).
Regarding claim 7, Li teaches the DNA binding protein (nCas9) is linked to TadA via a peptide linker comprising 32 amino acid residues (Fig. 1b, see STEME-1 and STEME-3).
Regarding claim 8, Li teaches the nucleotide sequence between Cas9 and TadA encodes a 32 amino acid peptide linker that has the sequence of SGGSSGGSSGSETPGTSESATPESSGGSSGGS (supplementary sequences 1) which is identical to the 32 AA residues in the instantly claimed 32 AA linker (see 112(b)).
Regarding claim 16, Li teaches introducing the composition into rice protoplasts via protoplast transfection mediated by polyethylene glycol (PEG) (p. 883, Methods section titled Protoplast transfection).
Regarding claim 17, Li teaches transforming binary vectors (encoding the dual-base editors) into Agrobacterium tumefaciens, then using Agrobacteirum-mediated transformation to introduce the vectors encoding the dual-base editor into rice calli (i.e. wherein the nucleic acid is delivered into plant cells by means of transformation using Agrobacterium tumefaciens) (p. 883, Methods section titled Agrobacterium-mediated transformation of rice callus cells).
It would therefore have been obvious to a person of ordinary skill in the art to combine the composition as taught by the co-pending applications with the teachings of Li to arrive at the instantly claimed method with a reasonable expectation of success because including the claimed and known linker peptides taught by Li, and introducing the composition or nucleic acid encoding the composition into plant cells by the claimed and known methods which are also taught by Li, may be achieved by one of ordinary skill without encountering any special technical difficulties. One of ordinary skill in the art would have been motivated to combine the teachings to arrive at the instantly claimed compositions because Li teaches using the linker peptides links the binding protein to TadA to successfully induce base edits (Fig. 1b, see STEME-1 and STEME-3), and further teaches the methods of introducing the composition or nucleic acid encoding the composition into the plant cell were also successful at inducing base edits (p. 883, Methods section titled Agrobacterium-mediated transformation of rice callus cells).
This is a provisional nonstatutory double patenting rejection.
Claim 15 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the specified claims above of copending Application Nos. 19/162,851, 19/497,215, 19/505,063, 19/396,735, 19/448,417, or 18/025,446 in view of Willis (WO-2021155065-A1, published 08/05/2021).
Application Nos. 19/162,851, 19/497,215, 19/505,063, 19/396,735, 19/448,417, or 18/025,446 each disclose the limitations of claim 1.
However, each of Application Nos. 19/162,851, 19/497,215, 19/505,063, 19/396,735, 19/448,417, or 18/025,446 do not explicitly disclose:
the composition according to claim 1, which does not comprise uracil DNA-glycosylase inhibitor (UGI) (claim 15).
Regarding claim 15, Molla teaches the limitations of claim 1-3 as set forth in the previous anticipation and obviousness rejections. The teachings of Molla as they are applied to claims 1-3 are set forth previously herein and are incorporated by reference.
However, Molla does not explicitly teach wherein the first split comprises the sequence from the N-terminus to at least one residue selected from the group consisting of G33, G44, A54, N68, G82, N98, and G108 of SEQ ID NO:1 (claim 4), nor wherein the second split comprises the sequence from at least one residue selected from the group consisting of G34, P45, G55, N69, T83, A99, and A109 to the C-terminus residue of SEQ ID NO: 1 (claim 5). This is because Molla does not explicitly identify the location of the DddA splits. Additionally, Molla provides a UGI in all Figures and examples, and therefore does not explicitly teach the composition according to claim 1, which does not comprise uracil DNA- glycosylase inhibitor (UGI).
Regarding claim 15, Willis teaches TALE-DddA constructs may be UGI-free (Fig. 8A-B and caption in ¶0072).
It would therefore have been obvious to a person of ordinary skill in the art to combine the composition as taught by the co-pending applications with the teachings of Willis to arrive at the instantly claimed method with a reasonable expectation of success because including or excluding a UGI from the composition as taught by Willis is a matter of experimental design and the composition in these various embodiments may be achieved without encountering any special technical difficulties. One of ordinary skill in the art would have been motivated to combine the teachings to arrive at the instantly claimed composition because Willis teaches the UGI-free TALE-split halves express well in cells (0072-0073 and Figs. 8-9).
Conclusion and Inquiries
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA N STOCKDALE whose telephone number is (703)756-5395. The examiner can normally be reached M-F 8:30-5:00 CT.
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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
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