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 .
Election/Restrictions
Applicant’s election without traverse of Group I Claims 1-10 and 16 in the reply filed on December 22, 2025 is acknowledged.
The restriction is made FINAL.
Claim Status
Claims 1-16 are pending. Claims 11-15 are withdrawn due to species election and not examined on its merits. Claims 1-10 and 16 are examined in the instant application.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No EP21306460.3, filed on October 19, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 30, 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
P.39 https://doi.org/10.1104/pp.112.196048
Appropriate correction is required.
Claim Objections
Claims 6 and 8 objected to because of the following: the recitation of “qRNA” is misspelled and it appears to mean “gRNA”. The claims need to be amended to --gRNA--.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)(Indefinite)
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 1-10 and 16, 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.
Claim 1 recites the limitation “left” and “right” “ubiquitin-like region” are unclear. Meanwhile, the specification defines the ubiquitin-like region as a sequence homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene (spec. p. 10 lines 1-14, image below).
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Additionally, the specification discloses that “By the expression ‘a sequence homologous to sequence X’, it is particularly meant that said sequence has at least 85% identity with sequence X” (spec. p. 10 lines 15-18).
This implies that in other embodiments “ubiquitin-like region” could include other undisclosed sequences or homologs, fragments, or variants having at least 85% sequence identity to an undisclosed sequence, which could be as little as a dinucleotide. The only ubiquitin-like region sequences that the specification discloses are SEQ ID NOs: 66-69 (p.25), however the claims are not limited to said sequences. Additionally, the Applicant does not define what the “left” and “right” ubiquitin-like region besides the “left ubiquitin-like region in 5' and a right ubiquitin-like region in 3' ” making unclear. For example, does it mean that they belong at the ends of the construct or are they fused to the gene of interest.
Because there is no definition for “left” and “right” “ubiquitin-like region” in the specification, the limitation has been defined by a function rather than a structure.
Furthermore, since the specification fails to disclose any of the structures found within “ubiquitin-like region” that confer functional activity, and the art disclose numerous functions for a “ubiquitin-like region”.
Therefore, the metes and bounds of the claim are indefinite because the structures of “ubiquitin-like region” as encompassed by the claim are unclear, and because the art as outlined infra describes that “ubiquitin-like region” have functions that differ from those as encompassed by the instant invention.
Claims 6 and 8 recite the same limitation and are therefore rejected for the same reason as provided for claim 1.
In regard to claim 1, the term “suitable” is unclear. Applicant has not properly defined the term suitable. Does applicant mean that the vector can be used in a plant or does it mean that the vector is able to comprise said repair DNA? The term suitable is subjective and need to be clarified. Therefore, it is advised to delete the term “suitable”.
Claims 2-5, 7, 9-10 and 16 are rejected for depending upon a rejected base claim and for failing to remedy the issues of indefiniteness.
Correction and/or clarification is required
Claim Rejections - 35 USC § 112(d)
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The recitation of “at least one polyubiquitin gene” in claim 16 is broader/encompasses more than the claim from which it depends. The issue is that claim 8 recites one/”the” polyubiquitin gene and claim 16 is more than one polyubiquitin gene such that it does not further limit but expands the claim from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)(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 1-10 and 16, 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.
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
The disclosure is as follows.
The specification describes targeting a polyubiquitin gene on Chr7DL of Chinese Spring (TraesCS7D01G443100) and identifies specific polyubiquitin target sequences for wheat (SEQ ID NOs: 3-5), in maize line B73 (SEQ ID NOs: 43-46), and Brassica napus (SEQ ID NOs: 57-59). The Applicant describes transforming wheat, maize, and B. napus with vectors comprising 1st gRNA target, a corresponding plant-specific left ubiquitin-like region, at least one gene of interest (GOI) such as (BAR, RFL29 or RFL79, ACCase, or ALS), a corresponding plant-specific right ubiquitin-like region, and 2nd gRNA target (examples 1-6).
Applicant describes that successfully increasing herbicide resistance using the BAR gene in wheat (p. 30 table 1) and the ALS gene (p.35 and fig. 9) as well as the restoration of fertility in wheat using RFL29 and RFL79 genes (p.32 line 19-21 and table 2).
The specification fails to describe a representative number of species or nucleic acid structures from the genus of ubiquitin-like region as broadly claimed.
The claimed invention lacks adequate written description for the following reasons. Claims 1-10 and 16 are directed to a vector comprising CRISPR/Cas9 editing system targeting the endogenous polyubiquitin gene in a plant. Additionally, these vectors comprise a repair DNA comprising of 1st gRNA target, left ubiquitin-like region, at least one GOI, right ubiquitin-like region, and 2nd gRNA target.
These ubiquitin-like region as a sequence homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene obtained from sources other than a plant, with structures and identities that are not disclosed. Because the specification does not adequately describe structures for ubiquitin like regions one would appreciate that Applicant doesn’t possess the genus of structures encompassed by the limitation “ubiquitin like region”.
From the disclosure of ubiquitin-like regions in the instant specification one skilled in the art cannot predict the structures of other ubiquitin-like regions genes or fragments from other sources and their allelic variants with ubiquitin-like regions that can effectively bind to an unknown polyubiquitin gene. Ubiquitin-like regions is a broad genus of structures/nucleic acid sequences which both the art and specification fail to define and are thus not described.
The ubiquitin-like regions encompass a broad genus of structures because the specification fails to define a ubiquitin-like region and only provides examples of ubiquitin-like regions as a sequence homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene (spec. p. 10 lines 1-14, image below). Additionally, the specification describes “By the expression ‘a sequence homologous to sequence X’, it is particularly meant that said sequence has at least 85% identity with sequence X” (spec. p. 10 lines 15-18).
The limited description of a few species of these polyubiquitin genes and ubiquitin-like regions are not representative of the ENTIRE and broad genus of polyubiquitin genes and ubiquitin-like regions as encompassed by the claims. Thus, there are insufficient relevant identifying characteristics to allow one skilled in the art to predictably determine the structures necessary to target the polyubiquitin genes for integration of a GOI or to determine the structures ubiquitin-like regions which retain functional activity for targeted integration in the broad genus of all plants as claimed.
Moreover, while one skilled in the art can generate sequences having at least the same structures of the polyubiquitin genes and ubiquitin-like regions as described in the specification, it is unpredictable which species within the genus of ubiquitin genes and ubiquitin-like regions as broadly claimed would also yield a functional vector for targeted integration of a gene of interest.
Here, “ubiquitin-like region” as claimed includes an exhaustive genus of sequences, homologs, fragments, or sequences having at least 85% sequence identity to any sequence found within the ubiquitin like region. This region is defined as being homologous to a sequence comprising the end of the polyubiquitin coding region and at least a portion of the 5’ and /or 3’ UTR; notably, these regions can be as little as a dinucleotide.
However, the only ubiquitin-like region sequences that the specification discloses are SEQ ID NOs: 66-69 (p.25) yet the claims are not limited to said sequences. Because there is no definition for “ubiquitin-like region” in the specification, the limitation has been defined by a function rather than a structure.
For example, Han et al. (“Regulation of polyubiquitin genes to meet cellular ubiquitin requirement.” BMB reports vol. 54,4 (2021): 189-195. doi:10.5483/BMBRep.2021.54.4.005 (U)) describes the different roles for polyubiquitin genes such as “Monoubiquitination is known to regulate histone modification, receptor endocytosis, etc. (3). Polyubiquitination plays different roles depending on the type of Ub chains (4). It is involved in a variety of cellular processes, such as proteasomal degradation, stress response, signal transduction, and membrane protein trafficking.” (p. 189 Introduction). This suggests that depending on the cellular processes the expression pattern of the gene will fluctuate.
This variability in function would not allow one skilled in the art to predictably produce ubiquitin-like regions that would target the integration of a gene of interest into a polyubiquitin gene as the art describes polyubiquitin gene function differs. Therefore, the specification has not described a representative number of species from the genus of ubiquitin-like regions necessary to target all polyubiquitin genes.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1-10 and 16 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 targeting a polyubiquitin gene on Chr7DL of Chinese Spring (TraesCS7D01G443100) and identifies specific target sequences for wheat (SEQ ID NOs: 3-5), in maize line B73 (SEQ ID NOs: 43-46), and Brassica napus (SEQ ID NOs: 57-59), 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 and 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.
(A) The breadth of the claims
The breadth of the claims encompasses any plant being genetically modified in the endogenous polyubiquitin gene with a vector comprising 1st gRNA target, left ubiquitin-like region, at least one any gene of interest (GOI), right ubiquitin-like region, and 2nd gRNA target, wherein the polyubiquitin and ubiquitin-like have any structure and function. However, the specification has only taught transforming wheat, maize, and B. napus with a vector comprising 1st gRNA target, a corresponding plant-specific left ubiquitin-like region, at least one gene of interest (GOI) such as (BAR, RFL29 or RFL79, ACCase, or ALS), a corresponding plant-specific right ubiquitin-like region, and 2nd gRNA target.
(B) The nature of the invention.
The nature of the claimed invention is directed to a vector comprising 1st gRNA target, left ubiquitin-like region, at least one any gene of interest (GOI), right ubiquitin-like region, and 2nd gRNA target, wherein the polyubiquitin and ubiquitin-like have any structure and function.
(C) The state of the prior art
The state of the prior art has taught that various polyubiquitin genes along with various roles see Han et al. 2021 above. Additionally, many of these polyubiquitin genes vary in structure and function.
(D) The level of one of ordinary skill
The level of one of ordinary skill in the art is high.
(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.
The claimed invention lacks adequate enabling guidance for the following reasons. Claims 1-10 and 16 are directed to a vector comprising CRISPR/Cas9 editing system targeting the endogenous polyubiquitin gene in a plant. Additionally, these vectors comprise a repair DNA comprising of 1st gRNA target, left ubiquitin region, at least one GOI, right ubiquitin region, and 2nd gRNA target.
These ubiquitin-like regions encompass sequences from non-plant sources with structures and functions that are not taught. The specification does not enable one skilled in the art to predict which ubiquitin-like regions will be functionally active. Consequently, producing a functional vector would require undue experimentation to test near-infinite combinations of these unknown structures to produce a functional vector.
The ubiquitin-like regions as claimed encompass a broad genus of structures because the specification teaches the ubiquitin-like region may be a sequence homologous to a sequence comprising the end of the coding region of the polyubiquitin gene and at least a portion of the 5’ and/or 3’ UTR of the polyubiquitin gene (spec. p. 10 lines 1-14, image below). Additionally, the specification teaches that “By the expression ‘a sequence homologous to sequence X’, it is particularly meant that said sequence has at least 85% identity with sequence X” of an undisclosed sequence (spec. p. 10 lines 15-18).
The limited guidance regarding the structures of polyubiquitin genes and ubiquitin-like regions does not allow one skilled in the art to predictably determine the structures required to target a gene of interest into a polyubiquitin gene in the broad genus of all plant as claimed without undue experimentation.
Moreover, while one skilled in the art can generate sequences having at least the same polyubiquitin genes and ubiquitin-like regions as taught in the specification, it is unpredictable which structures would predictably insert a gene of interest into the genus of polyubiquitin genes as claimed without undue experimentation.
Additionally, the limitation “ubiquitin-like region” includes other sequences or homologs, fragments, or variants having at least 85% sequence identity to structures within a polyubiquitin gene, which could be as little as a dinucleotide. The only ubiquitin-like region sequences that the specification teaches are SEQ ID NOs: 66-69 (p.25) yet however the claims are not limited to said sequences. Because there is no definition for “ubiquitin-like region” in the specification, the limitation has been defined by a function rather than a structure.
For example, Han et al. (“Regulation of polyubiquitin genes to meet cellular ubiquitin requirement.” BMB reports vol. 54,4 (2021): 189-195. doi:10.5483/BMBRep.2021.54.4.005 (U)) teaches the different roles such as “Monoubiquitination is known to regulate histone modification, receptor endocytosis, etc. (3). Polyubiquitination plays different roles depending on the type of Ub chains (4). It is involved in a variety of cellular processes, such as proteasomal degradation, stress response, signal transduction, and membrane protein trafficking.” (p. 189 Introduction).
This variability would not allow one skilled in the art to predictably produce ubiquitin-like regions for targeted integration of a gene of interest into polyubiquitin genes as broadly claimed. Therefore, the specification has not provided adequate working examples to practice the claimed invention.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples regarding the structure of ubiquitin-like regions which target all polyubiquitin genes, the state of the prior art, and unpredictability in the art, one skilled in the art cannot make and use the claimed invention as commensurate in scope with the claims without excessive burden and undue experimentation.
For at least this reason, the specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-10 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Baltes et al. (WO 2018/005589 (N)) in view of Do et al. (BMC Plant Biology (2019) 19:311 https://doi.org/10.1186/s12870-019-1906-8 (V)) and Hirai et al. (“Ubiquitin promoter–terminator cassette promotes genetically stable expression of the taste-modifying protein miraculin in transgenic lettuce” Plant Cell Rep 30, 2255–2265 (2011). https://doi.org/10.1007/s00299-011-1131-x.(W)).
Claim interpretation:
The Applicant does not define “left” and “right” “ubiquitin-like region” leaving room for interpretation. The Office interprets the terms as any sequence from a ubiquitin gene fused to both ends of the gene of interest, making a “ubiquitin sandwich” with the GOI in the middle.
In regard to claims 1-2, 4-5, 7, 9-10 and 16, Baltes et al. teach using a vector to target insertion of GmEPSPS, BAR or YFP genes downstream of GmUbi3 in soybean protoplast (claim 13 p. 42-44 ex. 2-4). Additionally, Baltes et al. teach having a left and right ubiquitin TALEN target DNA sequence (which the right/left ubiquitin-like region is being interpreted as a gene being inserted into the ubiquitin gene) (p.42 table 1, ex. 2 and Figs. 6-7).
Baltes et al. teach that “molecules designed to knockin GmEPSPS, Bar, or YFP into the GmUbi3 gene (3' insertion)” (i.e. at least one gene of interest in the 3’ of a polyubiquitin gene) (claim 4, p. 7 lines 10-11, ex. 2 and Figs. 6-7). Furthermore, when knocking in EPSPS gene it enhances herbicide tolerance (p.46-47 ex. 8). Lastly, Baltes et al. teach that CRISPR Cas9 systems can be used with said vector (p. 21 lines 17-32).
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Overall, Baltes et al. teach on a blueprint on how to target the endogenous ubiquitin gene.
In regard to 1-2, 4-5, 7, 9-10 and 16, Baltes et al. teach only on using one gRNA and do not teach using two CRISPR gRNAs.
In regard to claims 1-2, 4-5, 7, 9-10 and 16, Do et al. teach using “dual gRNA CRISPR/Cas9 system offers a rapid and highly efficient method to simultaneously edit” (pg.1 Abstract and Figs. 1 and 4). Do et al. teach knocking in mutations to the GmFAD gene resulting in 80% increase in oleic acid (Fig. 4). Lastly, Do et al. teach on specifically using “Cas9 expression construct for targeted mutagenesis, pSK-AtU6–26- gRNA1 was cut with BamHI-SpeI, pSK-AtU6–26- gRNA2 was cut with BamHI-EcoRI, and 35S-Cas9-SK was digested with HindIII-SpeI. These 3 fragments were assembled into pFGC5941 by HindIII-EcoRI restriction digestion followed by ligation to give the pFGC-GmFAD2-CRISPR construct.” (p.11). Overall, Do et al. demonstrates how a dual gRNA system can be used to effectively and efficiently genetically modify plants to improve crop performance.
In regard to 1-2, 4-5, 7, 9-10 and 16, Hirai et al. teach “that the ubiquitin promoter/terminator cassette is an efficient platform for the genetically stable expression” (p. 2256 Abstract). Specifically, Hirai et al. teach that “the endogenous lettuce ubiquitin promoter, fused to a ubiquitin terminator, is a suitable driver for stable foreign gene expression in lettuce and overcomes the gene silencing problem” (p.2263 col.2 last sentence) suggesting that endogenous ubiquitin-like regions were used in the vector to improve stable gene expression and confers gene activity of the gene of interest.
Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious for one of skill in the art to modify the teachings of Baltes et al. for targeted integration of a GOI into the endogenous polyubiquitin in Glycine max using a vector system (claim 13 p. 42-44 ex. 2-4) by instead using the dual gRNA system as taught by Do et al. because to do so is a simple addition of another gRNA instead on just one gRNA and offers a rapid and highly efficient method to simultaneously edit (pg.1 Abstract and Figs. 1 and 4). Along with the teachings of Hirai et al. fusing ubiquitin promoter and terminator to the gene of interest to stabilize gene expression and prevent gene silencing (p.2263 col.2 last sentence).
These methods of Baltes et al. and Do et al. are functionally each teach methods for introducing a gene of interest using CRISPR editing systems which are methods known to one of ordinary skill in the art and are used for the same purpose.
Additionally, Hirai et al. teach that the use of left and right ubiquitin-like regions in vector construction enables stable gene expression and prevention of gene silencing, yielding a predictable result.
One would have a reasonable expectation of success in doing so because of Baltes et al. and Do et al. successfully introduce mutations to improve crop performance.
Additionally, Hirai et al. teach how using left and right ubiquitin-like regions confers successful gene expression compared to traditional methods such CaMV 35S promoters.
Based on the teachings of Baltes et al. in view of Do et al. and Hirai et al., one would reasonably expect to produce a vector to introduce a gene of interest using dual gRNA targets and ubiquitin promoter/terminator cassette to target the endogenous polyubiquitin gene in plants to positively impact crop performance (claim 4, p. 7 lines 10-11, ex. 2 and 8, and Figs. 6-7).
Given that Baltes et al. and Do et al. teach using gRNAs to introduce a gene, along with using left and right ubiquitin-like regions to increase the likelihood of successful gene expression as taught by Hirai et al., it would have been obvious to combine the cited references knowing that one skilled the art can readily use vector construction techniques to introduce construct a vector comprising a first gRNA, a left ubiquitin-like region, a gene of interest, a right ubiquitin-like region, and a second gRNA to integrate a gene of interest into the endogenous polyubiquitin gene as taught by Baltes et al..
In regard to claim 3, both Baltes et al. and Do et al. do not teach on the vector comprising a single gRNA expression cassette. However, do to the high level of skill found in those ordinary artisan to choose from a single or multiple expression cassettes would be held to be an obvious matter of design choice, because the proposed modifications would merely have been expected to have the same functional properties as the prior art product.
In regard to claims 6 and 8, Baltes et al., Do et al., and Hirai et al. teach on transforming plants with said vector and editing systems (p. 43 ex. 3, p. 11 col.2, and p. 2257-2258, respectively).
Conclusion
No claims are allowed.
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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662