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 .
EXAMINER’S NOTE
Examiner has noted that the ADS filed on 04/16/2025 and the specification dated 04/16/2025 (paragraph 0001) have designated the instant application as a Divisional Application of U.S. Application No. 17/906,947, filed September 21, 2022. However, U.S. Application No. 17/906,947, as the parent application, does not contain a restriction requirement in the prosecution history. Therefore, the instant application cannot be a divisional application relative to U.S. Application No. 17/906,947. Thus, the examiner is treating the instant application as a continuation of U.S. Application No. 17/906,947. Examiner suggests that applicant submit a new ADS and amended specification to reflect this determination and redefine the relationship of these applications.
Priority
Acknowledgment is made of Applicant' s claim for domestic benefit under 35 U.S.C. 119(e). As such, the effective filing date of Claims 55-64 is March 30th, 2020.
Status of the Claims
Claims 55-64 are pending.
Claims 55-64 are examined herein.
Information Disclosure Statement
The Information Disclosure Statements filed on 06/18/2025 and 07/01/2025 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. Signed copies of the lists of references cited are included with this Office Action.
Specification
The disclosure is objected to because of the following informalities:
The use of the term TransMessenger, Stemfect, and TransIT on pg. 48; SNA on pg. 54, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claims 55-56, 60-61, and 64 are objected to because of the following informalities:
Claim 55 recites the term “LbCpf1” which is not a defined acronym. As Claim 55 is the first recitation of “LbCpf1” in the claim set, Applicant is advised to clearly define the full name of the acronym.
Claim 55, part (ii) should be amended to recite “the sCAI of the
Claim 56, line 3 should be amended to recite “…said synthetic polynucleotide…”
Claims 55-56, 60, and 64 should be amended to recite “…a guanine and cytosine (GC)
Claim 61 recites, in part, “…selected from:…” from which a list of alternative follows. If this recitation is meant to be a Markush group, then Claim 61 is not written in proper Markush format. The claim should be in the format “selected from the group consisting of A, B, C, and D”. Instant Claim 61 recites “and/or” rather than “and” after the second to last alternative member in the Markush group. See MPEP § 2173.05(h).
Appropriate correction is required.
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.
Claims 55-64 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. All dependent claims are included in these rejection unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend.
Claim 55, part (i) recites the limitation "the sCAI of the soybean codon-optimized reference polynucleotide of SEQ ID NO: 74" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim. Claim 55 does not recite a soybean codon-optimized reference polynucleotide prior to step (i), much less the specific polynucleotide set forth in SEQ ID NO: 74. Therefore, the metes and bounds of the claimed invention are unclear. To overcome this aspect of the indefiniteness rejection, Claim 55 part (i) should be amended to recite, for example, “…the sCAI of a soybean codon-optimized reference polynucleotide comprising the nucleotide sequence of SEQ ID NO: 74” for proper antecedence.
Claim 56, part (a) recites the limitation "the sCAI of the soybean codon-optimized reference polynucleotide of SEQ ID NO: 74" in line. There is insufficient antecedent basis for this limitation in the claim. Claim 56 does not recite a soybean codon-optimized reference polynucleotide prior to part (a), much less the specific polynucleotide set forth in SEQ ID NO: 74. Therefore, the metes and bounds of the claimed invention are unclear. To overcome this aspect of the indefiniteness rejection, Claim 56 part (a) should be amended to recite, for example, “…the sCAI of a soybean codon-optimized reference polynucleotide comprising the nucleotide sequence of SEQ ID NO: 74” for proper antecedence.
Claim 59 recites the limitation "the target editing site" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 56, from which Claim 59 depends, does not recite the term “target editing site” or any variant thereof, and as such, the metes and bounds of the claimed invention are unclear. To overcome this aspect of the indefiniteness rejection, Claim 59 should be amended to recite, for example, “…to a target editing site” for proper antecedence.
Claim 64, part (a) recites the limitation "the synthetic polynucleotide" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 64 does not recite a synthetic polynucleotide prior to part (a) in the preamble, much less a synthetic polynucleotide encoding the protein comprising the LbCpf1 RNA-guided endonuclease (RGE) or the LbCpf1 RNA-guided nickase (RGN) having at least 99% sequence identity to SEQ ID NO: 73. Therefore, the metes and bounds of the claimed invention are unclear. To overcome this aspect of the indefiniteness rejection, Claim 64 part (a) should be amended to recite, for example, “…a synthetic polynucleotide…” for proper antecedence.
Claim Rejections - 35 USC § 112
Written Description
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 56-63 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. All dependent claims are included in these rejections unless they contain a limitation that overcomes the deficiencies of the parent claim from which they depend.
Claims 56-63 require a synthetic polynucleotide encoding an LbCpf1 RNA-guided endonuclease or an LbCpf1 RNA-guided nickase having at least 99% sequence identity relative to SEQ ID NO: 73, wherein the said synthetic polynucleotide has more than 80% identity across the entire length of instant SEQ ID NO: 75.
Polynucleotides with 80% identity to the 3684 base pair long instant SEQ ID NO: 75 encompass polynucleotides with approximately 737 nucleic acid substitutions, additions, or deletions relative to SEQ ID NO: 75. Polynucleotides with 737 nucleic acid substitutions, additions, or deletions relative to SEQ ID NO: 75 encompass approximately 4(737 x 3!) unique polynucleotides, of which Applicant does not appear to be in possession of at the time of filing.
The instant application fails to provide guidance for which nucleic acids of SEQ ID NO: 75 can be altered and/or duplicated, and to which nucleic acids, as well as failing to provide guidance for which nucleic acids must not be changed, to maintain the functional activity of the synthetic polynucleotide when it is introduced into a soybean plant cell and the functional activity of the encoded LbCpf1 RNA-guided endonuclease or LbCpf1 RNA-guided nickase having at least 99% sequence identity relative to SEQ ID NO: 73, which is comprised within the synthetic polynucleotide. The specification also fails to provide guidance for which nucleic acids can be deleted and which region of the sequence can tolerate insertions and still have expression activity in a soybean plant cell as well as expression activity of the encoded LbCpf1 RNA-guided endonuclease or LbCpf1 RNA-guided nickase having at least 99% sequence identity relative to SEQ ID NO: 73 which are comprised within the synthetic polynucleotide. The specification does not provide adequate guidance with respect to expression, biological activity, or modifying the functional activity of the claimed genera of synthetic polynucleotides.
The instant specification discloses SEQ ID NO: 75 (pg. 19, Table 7), but does not disclose any polynucleotides with 80-99% sequence identity relative to SEQ ID NO: 75. The other polynucleotides disclosed in the specification have less than 75.1% sequence identity to instant SEQ ID NO: 75 (See sequence alignments located in 20260527_085012_us-19-180-744-75.rnpbm within the file wrapper).
A Geneseq search of instant SEQ ID NO: 75 did not disclose any prior art accessions with 80-100% sequence identity and 100% query coverage to instant SEQ ID NO: 75. The closest prior art accession to instant SEQ ID NO: 75 was Geneseq Accession BEH29050 (dated 10/19/2017) an L. bacterium ND2006 LbCpf1 human codon optimized DNA with 76.8% sequence identity relative to SEQ ID NO: 75 (See Result 16 of 20260527_085012_us-19-180-744-75.rng in the file wrapper).
An EST search of instant SEQ ID NO: 75 did not disclose any prior art accessions with 80-100% sequence identity and 100% query coverage of SEQ ID NO: 75. The closest prior art accession to instant SEQ ID NO: 75 was EST Accession GA512283 (dated 07/02/2013) with 3.3% sequence identity relative to SEQ ID NO: 75 (See Result 1 of 20260527_085012_us-19-180-744-75.rst in the file wrapper).
Additionally, a search of the patent literature reveals that there is no well-developed field of prior art regarding polynucleotides with 80-100% sequence identity and 100% query coverage relative to SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome (See all results found in 20260527_085012_us-19-180-744-75.rni and 20260527_085012_us-19-180-744-75.rnpbm located in the file wrapper).
Therefore, based on a search of the patent and non-patent literature, there is no well-developed field of prior art for polynucleotides having 80-100% sequence identity and 100% query coverage relative to instant SEQ ID NO: 75, much less sequences 80-100% sequence identity and 100% query coverage relative to instant SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome.
The specification does not disclose any functional fragments or biologically active fragments of instant SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome. Additionally, the prior art does not teach these functional fragments or biologically active fragments specific to polynucleotides with 80-99% sequence identity to SEQ ID NO: 75.
The specification does not disclose the functional or biologically active fragments that distinguish polynucleotides with at least 80% identity to SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome from other polynucleotides with at least 80% identity to SEQ ID NO: 75 that do not function to modify an endogenous soybean gene in a soybean genome.
One of ordinary skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species. Since the
disclosure fails to describe the common attributes that identify members of the genus, and because the
genus is both vast and highly diverse, SEQ ID NO: 75 is insufficient to describe the claimed genus.
The number of species described by Applicant are insufficient to describe the recited genus by virtue of example, given the vast size of the recited genus and the lack of written description in the
instant specification with regard to the structural and functional characteristics of the claimed
compositions.
Hence, Applicant has not, in fact, described the claimed methods within the full scope of the claims, and the specification fails to provide an adequate written description of the claimed invention.
Claim Rejections - 35 USC § 112
Scope of Enablement
Claims 56-63 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a synthetic polynucleotide that has 100% identity across the entire length of SEQ ID NO: 75, does not reasonably provide enablement for a synthetic . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513
(Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404
(Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
Claims 56-63 generically require the broad genus of synthetic polynucleotides having more than 80% identity across the entire length of instant SEQ ID NO: 75, also comprising an LbCpf1 RNA-guided endonuclease or an LbCpf1 RNA guided nickase having at least 99% identity relative to instant SEQ ID NO: 73. Applicant does not teach how to make or use synthetic polynucleotide sequences having at least 80% sequence identity across the entire length of SEQ ID NO: 75 that elicit the recited function modifying an endogenous soybean gene in a soybean genome, much less synthetic polynucleotide sequences having at least 80% sequence identity across the entire length of SEQ ID NO: 75 comprising an LbCpf1 RNA-guided endonuclease or an LbCpf1 RNA guided nickase having at least 99% identity relative to instant SEQ ID NO: 73 that elicit the recited function modifying an endogenous soybean gene in a soybean genome.
Polynucleotides with 80% identity to the 3684 base pair long instant SEQ ID NO: 75 encompass polynucleotides with approximately 737 nucleic acid substitutions, additions, or deletions relative to SEQ ID NO: 75. Polynucleotides with 737 nucleic acid substitutions, additions, or deletions relative to SEQ ID NO: 75 encompass approximately 4(737 x 3!) unique polynucleotides, of which Applicant does not appear to be in possession of at the time of filing.
The instant application fails to provide guidance for which nucleic acids of SEQ ID NO: 75 can be altered and/or duplicated, and to which nucleic acids, as well as failing to provide guidance for which nucleic acids must not be changed, to maintain the functional activity of the synthetic polynucleotide when it is introduced into a soybean plant cell and the functional activity of the encoded LbCpf1 RNA-guided endonuclease or LbCpf1 RNA-guided nickase having at least 99% sequence identity relative to SEQ ID NO: 73, which is comprised within the synthetic polynucleotide. The specification also fails to provide guidance for which nucleic acids can be deleted and which region of the sequence can tolerate insertions and still have expression activity in a soybean plant cell as well as expression activity of the encoded LbCpf1 RNA-guided endonuclease or LbCpf1 RNA-guided nickase having at least 99% sequence identity relative to SEQ ID NO: 73 which are comprised within the synthetic polynucleotide. The specification does not provide adequate guidance with respect to expression, biological activity, or modifying the functional activity of the claimed genera of synthetic polynucleotides.
The instant specification teaches SEQ ID NO: 75 (pg. 19, Table 7), but does not teach any polynucleotides with 80-99% sequence identity relative to SEQ ID NO: 75. The other polynucleotides disclosed in the specification have less than 75.1% sequence identity to instant SEQ ID NO: 75 (See sequence alignments located in 20260527_085012_us-19-180-744-75.rnpbm within the file wrapper).
A Geneseq search of instant SEQ ID NO: 75 did not teach any prior art accessions with 80-100% sequence identity and 100% query coverage to instant SEQ ID NO: 75. The closest prior art accession to instant SEQ ID NO: 75 was Geneseq Accession BEH29050 (dated 10/19/2017) an L. bacterium ND2006 LbCpf1 human codon optimized DNA with 76.8% sequence identity relative to SEQ ID NO: 75 (See Result 16 of 20260527_085012_us-19-180-744-75.rng in the file wrapper).
An EST search of instant SEQ ID NO: 75 did not teach any prior art accessions with 80-100% sequence identity and 100% query coverage of SEQ ID NO: 75. The closest prior art accession to instant SEQ ID NO: 75 was EST Accession GA512283 (dated 07/02/2013) with 3.3% sequence identity relative to SEQ ID NO: 75 (See Result 1 of 20260527_085012_us-19-180-744-75.rst in the file wrapper).
Additionally, a search of the patent literature reveals that there is no well-developed field of prior art regarding polynucleotides with 80-100% sequence identity and 100% query coverage relative to SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome (See all results found in 20260527_085012_us-19-180-744-75.rni and 20260527_085012_us-19-180-744-75.rnpbm located in the file wrapper).
Therefore, based on a search of the patent and non-patent literature, there is no well-developed field of prior art for polynucleotides having 80-100% sequence identity and 100% query coverage relative to instant SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome, much less polynucleotides having 80-100% sequence identity and 100% query coverage relative to instant SEQ ID NO: 75 comprising an LbCpf1 RNA-guided endonuclease or an LbCpf1 RNA guided nickase having at least 99% identity relative to instant SEQ ID NO: 73 that elicit the recited function modifying an endogenous soybean gene in a soybean genome.
Thus, from the guidance in the specification, it would appear that one of ordinary skill in the art would be required to produce the claimed synthetic polynucleotides by making random nucleotide deletions, substitutions, and insertions, which would be unpredictable.
Making insertions, deletions and substitutions relative to SEQ ID NO: 75 while retaining the activity to modify an endogenous soybean gene is unpredictable. These insertions, deletions, and substitutions in the polynucleotide encoded by SEQ ID NO: 75 would in many cases result in a change in the amino acids they encode and the resulting polypeptide. The amino acid, which is the primary structure of the polypeptide, is the basis for the spatial structure of the polypeptide, which in turn directly determines its function. Even small changes in the amino acid sequences produced by SEQ ID NO: 75 may lead to large changes in spatial structure, in turn altering the function of the polypeptide. Such differences in sequence structure will result in changes or even loss of function in certain nucleic acids/polypeptide molecules. While it is known that many amino acid substitutions, additions or deletions are generally possible in any given protein, the positions within the protein’s sequence where such amino acid changes can be made with a reasonable expectation of success (without altering protein function) are limited. Certain positions in the sequence are critical to the protein’s structure/function relationship, for example various sites or regions directly involved in binding, activity, and in providing the correct three-dimensional spatial orientation of binding and active sites. These regions can tolerate only relatively conservative substitutions or no substitutions at all. See Keskin et al., 2004, Protein Science 13: 1043-1055 (IDS Document), which teaches that proteins with similar structure may have different functions (Abstract; pages 1043-1044). See also Guo et al., 2004, Proceedings of the National Academy of Sciences USA 101: 9205-9210 (IDS Document), which teaches that there is a probability factor of 34% that a random amino acid replacement in a given protein will lead to its inactivation (Abstract; page 9206; Table 1). In the instant case, such a probability factor will be much higher as the claims encompass more than a single amino acid change in the proteins encoded by the polynucleotides comprising SEQ ID NO: 75. Furthermore, Thornton et al. (2000) (Nature Structural Biology, structural genomic supplement, November 2000: 991-994; IDS Document), teaches that structural data may carry information about the biochemical function of a protein, while its biological role in the cell or organism is much more complex and additional experimentation is needed to elucidate actual biological function (page 992, left column, paragraph 2).
Undue experimentation would be required by one of ordinary skill in the art to make and use all nucleic acid molecules having at least 80% sequence identity to instant SEQ ID NO: 75 that would still retain the function of the encoded synthetic polypeptide.
Additionally, the structure/function relationship that distinguishes synthetic polynucleotides with at least 80% identity to SEQ ID NO: 75 that function to modify an endogenous soybean gene in a soybean genome from other polynucleotides with at least 80% identity to SEQ ID NO: 75 that do not modify an endogenous soybean gene in a soybean genome are unknown. Accordingly, the specification does not provide a representative number of species to adequately enable the use of the broadly claimed genus of all possible claimed synthetic polynucleotides containing the sequence having at least 80% identity relative to instant SEQ ID NO; 75, also comprising an LbCpf1 RNA-guided endonuclease or an LbCpf1 RNA guided nickase having at least 99% identity relative to instant SEQ ID NO: 73. The specification does not provide adequate guidance with respect to expression, biological activity, or modifying the functional activity of the claimed genera of synthetic polynucleotides.
Given the claim breath, the unpredictability discussed above, undue experimentation, and lack of guidance in the specification as discussed above, the instant invention is not enabled throughout the full scope of the claims.
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.
Claim 55 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cai et al. (PLoS One 10.8 (2015): e0136064).
Regarding the broadest reasonable interpretation of Claim 55, it is noted in Claim 55 part (a) that the limitation which recites, in part, “a donor template DNA molecule having homology to the target editing site into a soybean plant cell comprising a synthetic polynucleotide encoding an LbCpf1 RNA-guided endonuclease (RGE) or LbCpf1 RNA guided nickase (RGN) having at least 99% sequence identity to SEQ ID NO: 73…” [this limitation continues into Claim 55 parts (i)and (ii)] is preceded by the phrase “and optionally”. Due to the recitation of “and optionally”, the claim limitation recited above and the claim limitations recited in parts (i) and (ii) are alternative limitations of Claim 55 that can be included in the scope of claim, without the claim necessarily requiring them. Therefore, the broadest reasonable interpretation of Claim 55 encompasses methods of modifying endogenous soybeans wherein a guide RNA or a polynucleotide encoding a guide RNA is directed to a target editing site in the endogenous soybean gene and selecting a modified soybean plant cell, soybean plant, soybean plant part, soybean tissue, or soybean callus comprising a modification of the endogenous soybean gene.
Regarding Claim 55, Cai et al. (herein referred to as Cai) discloses a method that modifies endogenous soybean genes using a type II CRISPR/Cas9 system to generate and estimate genome editing in the desired target genes in soybean (Glycine max (L.) Merrill.) plant cells. Cai discloses single-guide RNA (sgRNA) and Cas9 cassettes that were assembled on one vector to improve transformation efficiency, using six sgRNAs that targeted different sites of two endogenous soybean genes (GmFEI2 and GmSHR). Cai discloses that the targeted DNA mutations were detected in selected soybean hairy roots (a soybean plant cell/plant/part/tissue) (Abstract; Results, Target Site Selection and Construction of the SgRNA: Cas9 Expression Vector, paragraph bridging pgs. 4-5; Fig. 2 and Fig. 3; Table 1).
As such, this disclosure of Cai anticipates the instant invention.
Closest Prior Art
The closest prior art in regard to Claims 56-64 can be found in the combination of Cigan et al. (US 2018/0273960 A1, published 09/27/2018, IDS Document) in view of GenBank Accession KY985375.1 (dated 09/21/2017).
Cigan et al. teaches a method for modifying a nucleotide sequence in the genome of a plant cell without the use of a selectable marker, the method comprising: introducing into at least one plant cell a guide RNA/Cas9 endonuclease complex capable of making a double strand break in a target site located in said nucleotide sequence; and, selecting a plant cell having a modification in said nucleotide sequence, wherein the selection occurs without the use of a selectable marker (Claim 1), wherein the plant cell is selected from the group consisting of a maize, rice, sorghum, rye, barley, wheat, millet, oats, sugarcane, turfgrass, or switchgrass, soybean, canola, alfalfa, sunflower, cotton, tobacco, peanut, potato, tomato, tobacco, Arabidopsis, and safflower cell (Claim 22), and the method for modifying a nucleotide sequence in the genome of a plant cell without the use of a selectable marker further comprising introducing a donor DNA to the plant cell of (a) wherein said donor DNA comprises at least one polynucleotide of interest to be inserted into said target site (Claim 7), wherein the structural similarity between a given genomic region and the corresponding region of homology found on the donor DNA can be any degree of sequence identity that allows for homologous recombination to occur (pg. 15, paragraph 0113).
GenBank Accession KY985375.1 (dated 09/21/2017) teaches a synthetic construct clone pCSN067 comprising a Cpf1 gene derived from Lachnospiraceae bacterium ND2006 (LbCpf1) which has 99% query coverage and 77.46% sequence identity relative to instant SEQ ID NO: 75, as shown in the alignment attached to the file wrapper (See GenBank Accession KY985375.1). However, GenBank Accession KY985375.1 has a GC content of 43.0 %, and a basic melting temperature of 80°C as shown in the following figure:
PNG
media_image1.png
657
772
media_image1.png
Greyscale
Additionally, the combination of Cigan et al. and GenBank Accession KY985375.1 does not teach the feature of Claims 56, 60 and 64 wherein said synthetic polynucleotide has a soybean codon adaptation index (sCAI) which is decreased by a value of 0.02 to 0.03 in comparison to the sCAI of a soybean codon-optimized reference polynucleotide of SEQ ID NO: 74. Cigan et al. instead teaches the use of "plant-optimized nucleotide" sequences where "G-C content of the sequence may be adjusted to levels average for a given plant host, as calculated by reference to known genes expressed in the host plant cell" (paragraph 0396-0397). Cigan et al. describes a" "codon-modified gene" or "codon-preferred gene" or "codon-optimized gene" is a gene having its frequency of codon usage designed to mimic the frequency of preferred codon usage of the host cell” (paragraph 0165). Cigan et al. also incorporates by reference U.S. Patent No. 5,380,831 which states that ''the synthetic gene is designed such that its distribution frequency of codon usage deviates, preferably, no more than 25% from that of highly expressed plant genes and, more preferably, no more than about 10%" and "that consideration is given to the percentage G+C content of the degenerate third base (monocotyledons appear to favor G+C in this position, whereas dicotyledons do not)" (U.S. Patent No. 5,380,831, column 4, lines 20-29). As such, Cigan et al. does not suggest or provide any rationale for the use of a synthetic polynucleotide such as GenBank Accession KY985375.1 in a soybean plant which differs from the soybean codon-optimized reference sequences by using fewer soybean preferred codons than are found in a typical soybean. In fact, Cigan et al. teaches away from the use of sequences such as GenBank Accession KY985375.1 which are not designed based on the preferred codon usage of soybean.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KELSEY L. MCWILLIAMS whose telephone number is (703)756-4704. The examiner can normally be reached M-F 08:00-17:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, AMJAD ABRAHAM can be reached at (571) 270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KELSEY L MCWILLIAMS/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
Prosecution Insights