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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-21 and 37-41 in the reply filed on April 6, 2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). This Election/Restriction Requirement is made FINAL.
Claims 1-45 are pending. Claims 22-36 and 42-45 are withdrawn from consideration. Claims 1-21 and 37-41 are examined on their merit herein.
Claim Rejections - 35 USC § 112
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 1-21 and 37-41 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 is rejected as being indefinite for the recitation in item (ii), “compared to a control plant cell not comprising such oligonucleotides”. Since item (ii) is recited as independent alternatives of (i), and that item (ii) does not recite any “oligonucleotides”, and that item (ii) is drawn to a heat treatment, it is not clear why and how the heat treated samples should be “compared to a control plant cell not comprising such oligonucleotides”. The metes and bounds are not clear. Dependent claims 2-21 and 37-41 are also included in this rejection since they do not address this deficiency.
Claim 6 is rejected as being indefinite for the recitation of “wherein the chromosomal modification is between two homologous chromosomes” because the meaning is not clear. It is not clear if either one or both of the chromosomes has to be modified or whether the modification has to be originated from the two chromosomes, or whether it has to be one chromosome modifying the other.
Claims 20-21 are rejected as being indefinite for the recitation of “providing” to the crop plant cell one morphogenic factor or a BBM or WUS polypeptide as a morphogenic factor. It is not clear what is encompassed by “providing”, i.e., whether an external application of a solution to the growth medium is one way of “providing”? Or other transgenic means besides gene editing? The metes and bounds are not clear.
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 1-3, 7-10, 13-18, 20, and 37-41, are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (Scientific reports 6.1 (2016): 23890) in view of Kim (PGPUB US 20210040505A1, published Feb. 11, 2021, PCT filing date Jan. 11, 2019).
Claim 1 is drawn to a method of high-efficiency chromosomal modification in a crop plant cell, wherein the chromosome comprises a genomic target site, the method comprising:
(i) providing the plant cell with a DNA break inducing agent, one or more oligonucleotides with substantial sequence similarity to one or more chromosomal ends at
two different or distinct double strand break regions, and wherein the one or more oligonucleotides increase chromosomal modification efficiency at the genomic target site
by facilitating DNA end-joining, compared to a control plant cell not comprising such
oligonucleotides; or
(ii) providing the plant cell with a DNA break inducing agent designed to bind and cleave the genomic target site, wherein the plant cell is incubated at a temperature of at least about 28°C such that the higher temperature effect increases chromosomal modification efficiency at the genomic target site by facilitating DNA end-joining, compared to a control plant cell not comprising such oligonucleotides; or
(iii) providing the plant cell with a DNA break inducing agent that is engineered to bind and recurrently cleave the genomic target site such that the cleaved chromosomal ends at the genomic target site remain accessible for a substantially longer time to enable chromosomal modification at the genomic target site by facilitating DNA end-joining, compared to a control plant cell not comprising the recurrent cutting DNA break inducing agent;
wherein the chromosomal modification is a rearrangement, deletion, duplication, translocation, and/or an inversion of a large segment of the chromosome.
Regarding claim 1, Zhao teaches targeted gene replacement in plants using a dual-sgRNA/Cas9 design (Title). The method comprising providing to a plant cell a CRISPR/Cas9 construct which encodes a Cas9 nuclease (which reads in the claimed “providing the plant cell with a DNA break inducing agent”) that is designed to bind and cleave a target genomic region (Fig. 1, e.g.).
Zhao teaches the resulted chromosomal modification is successfully deletion of a target gene segment of ~950 bp with high efficiency in plants (p. 6, bottom). It should be noted that Zhao considered the deletion of this size to be “large DNA deletion” (p. 9, para. 4) . Moreover, although the instant Specification states “[I]n another embodiment, there are at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 900 or 1000 nucleotides between the at least one nucleotide to be edited.” Or “[I]n some aspects, the chromosomal segment is at least about 1 kb…..”. Due to the non-limiting language of “in another embodiment” or “in some aspects”, it is construed that the recited “is a rearrangement, deletion, duplication, translocation, and/or an inversion of a large segment of the chromosome” does not exclusively limit the deletion to be more than 1 kb. In this sense, Zhao teaches the large deletion of a chromosome segment that meets the limitation of the claim.
However, Zhao also further teaches that “parallel studies of Zea mays, which is an important cereal crop, also showed that the intentional deletion length could be flexible, ranging from 1 to 300 kb (data not shown)” (p. 6, bottom). Therefore, Zhao also teaches large deletion (300 kb) in maize (“crop plant”). Furthermore, Zhao also teaches that the CRISPR/Cas9 system should be a versatile tool for creating flexible deletion mutations ranging from 1 bp to an entire chromosome arm.
Zhao also teaches the targeted mutations in maize tend to be generated in the embryonic stage.
Zhao also teaches, two “homology arms” (Fig. 1) of 733 and 825 bp in length, that reads on the claimed “one or more oligonucleotides with substantial sequence similarity to one or more chromosomal ends at two different or distinct double strand break region”. By inserting a different gene at the edited locus, the edited chromosomal is “rearranged”.
Regarding claim 13, Zhao teaches the two DSB sites at a “sufficient distance to generate polymorphism.”
Regarding claims 37-38, Zhao teaches delivery by a vector (Fig. 1), and the two arms (oligonucleotides) are flanked by sgRNAs (the target sequences that contain a PAM for a CRISPR-Cas polypeptide to recognize and bind).
Regarding claims 39 and 41, Zhao teaches the release of the donor template molecule by Cas9 cleavage (Fig. 1).
Zhao does not teach the plant cell is incubated at a temperature of at least about 28°C such that the higher temperature effect increases chromosomal modification efficiency.
Kim teaches methods for increasing the efficiency of homologous recombination-based gene editing in a plant that includes optimizing temperature (Abstract), wherein the temperature conditions of the tissue culture are cultivation at 29 to 33° C for the first 4 to 6 days (Claim 2).
Regarding claim 20, Kim teaches inserting an ANT1 gene which confers purple color to the edited plant, thus reading on the recited “morphogenic factor”.
It would have been prima facie obvious and within the scope of a person having ordinary skills in the art at the time of the filing of the instant application to have combined the teachings of Kim with Zhao and arrive at the instantly claimed invention. The PHOSITA would have been motivated to use the high temperature treatment of Kim to increase the genome editing efficiency in the method of Zhao, to achieve deletions of large segments such as 300kb in size or potentially up to an arm of a chromosome. The PHOSITA would have had reasonable expectation of success given the teachings and success of both Zhao and Kim.
Therefore, the claimed invention as a whole is prima facie obvious over the combined teachings of the prior art.
Claims 1, 4, 6, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (Scientific reports 6.1 (2016): 23890) and Kim (PGPUB US 20210040505A1, published Feb. 11, 2021, PCT filing date Jan. 11, 2019) as applied to claim 1, and in view of Schmidt-2020 (aBIOTECH (2020) 1:21–31) with evidence from Schmidt-2019 (The Plant Journal (2019) 98, 577–589).
Claim 18 is drawn to the method of claim 1 wherein the plant cell is an egg cell. Claim 19 is drawn to the method of claim 1, wherein the DNA break inducing agent is expressed under the control of an egg cell promoter.
Zhao and Kim do not teach an egg cell promoter or editing in egg cell.
Schmidt-2020 teaches CRISPR-mediated restructuring plant chromosomes that resulted in chromosomal rearrangements (CRs), which are defined as ‘‘rearrangement of the linear sequence of chromosomes including transposition, duplication, deletion, inversion or translocation”; by inducing (one) or two DSBs at an identical position in homologues, crossovers can be achieved by HR or NHEJ (e.g., Fig. 2); the introducing two DSBs reads on the instantly recited method using two different or distinct double strand break regions. Schmidt-2020 teaches efficient inversion formation in Arabidopsis was conducted, where inversions up to 18 kb were successfully transmitted to the next generation using an egg cell-specific promoter for Cas9 expression which is taught in detail in Schmidt-2019.
It would have been prima facie obvious and within the scope of a person having ordinary skills in the art at the time of the filing of the instant application to have combined the teachings of Schmidt with Kim and Zhao and arrive at the instantly claimed invention. The PHOSITA would have been motivated to use the egg specific promoter of Schmidt to increase the genome editing efficiency (e.g., achieving editing in one generation). The PHOSITA would have had reasonable expectation of success given the teachings and success of Schmidt, Zhao and Kim.
Therefore, the claimed invention as a whole is prima facie obvious over the combined teachings of the prior art.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (Scientific reports 6.1 (2016): 23890) and Kim (PGPUB US 20210040505A1, published Feb. 11, 2021, PCT filing date Jan. 11, 2019) as applied to claim 1, and in view of Svitashev (Nature communications 7.1 (2016): 13274.)
Claims 20-21 are drawn to the method of claim 1 and wherein the plant cell is “provided” with a morphogenic factor such as WUS.
Zhao and Kim do not teach a WUS.
Svitashev teaches co-delivery of DNA vectors encoding ‘helper genes’—cell division promoting transcription factors (maize ovule developmental protein 2 (ODP2) and maize Wuschel (WUS) with the CRISPR/Cas for improved genome editing.
It would have been prima facie obvious and within the scope of a person having ordinary skills in the art at the time of the filing of the instant application to have combined the teachings of Svitashev with Kim and Zhao and arrive at the instantly claimed invention. The PHOSITA would have been motivated to use the cell division promoting transcription factor “helpers” of Svitashev to increase the genome editing efficiency. The PHOSITA would have had reasonable expectation of success given the teachings and success of Svitashev, Zhao and Kim.
Therefore, the claimed invention as a whole is prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed.
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WEIHUA . FAN
Primary Examiner
Art Unit 1663
/WEIHUA FAN/ Primary Examiner, Art Unit 1663
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