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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/8/2026 has been entered.
Election/Restrictions
Group 2 (claims 12-16 & 34-38) has been rejoined, because the subject matter falls within the subject matter of amended claims 1-11 & 29-33 of Group I. The shift to another invention after election results in no additional burden (MPEP 819).
Claims 26-28 remain withdrawn.
Status of Claims
Claims 1, 7-16 & 29-38 are under examination on the merits.
Claims 26-28 are withdrawn.
The objection to claim 1 is withdrawn in light of Applicant’s amendment.
The rejection of claim(s) 1, 7-11, 29-30 & 33 under 35 U.S.C. 103 as being unpatentable over Schmidt and Bundock and further in view of Boutilier et al (2002) The Plant Cell. 14: 1737–1749 (hereafter Boutilier) is withdrawn in light of Applicant’s amendments.
The provisional rejection of claims 1, 7-9 & 11 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 9, 10, 14, 28, 29, & 34 of copending Application No. 18/713,877 in view of et al (2019) The Plant Journal. 98:577-589 is withdrawn in light of Applicant’s amendments.
Claim Objections
Claims 12 & 35 are objected to because of the following informalities:
Claim 12 (line 3): “stand” should read --strand--.
Claim 35 (line 2) recites BBM and WUS. Abbreviations for gene names should be written out in full at first use.
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 12-16 & 34-38 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 36 recites the limitation "the Cas endonuclease" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 12 recites a double strand break inducing agent capable of site-specifically cleaving first and second target sites (lines 3-4) but does not recite a Cas endonuclease.
Claim 37 recites the limitation "the guide RNA" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 12 does not recite guide RNA.
Claim 12 recites the chromosomal segment inversion is “heterologous to its chromosome” (line 8). The instant specification defines “heterologous” as the difference between the original environment, location, or composition of the polynucleotide sequence and its current environment, location, or composition, and, in reference to a sequence, can refer to one that originates from a different species or variety or is substantially modified from its native form in composition and/or genomic locus (paragraph [0078]). It is unclear from this limitation whether the heterologous segment inversion must originate from a different chromosome, or a different location in the chromosome, than where it is found as a result of the claimed method, or if a segment inversion would be heterologous if it comprises mutations or genetic material not found in the endogenous chromosome. Because the scope of the limitation of segment inversions heterologous to a chromosome is unclear, claim 12 and dependent claims 13-16 & 34-38 are indefinite.
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.
Claim(s) 12 & 15 are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt et al (2019) The Plant Journal. 98:577-589 (published 3/22/2019, hereafter Schmidt) in view of Seah et al (2004) Theor Appl Genet. 108:1635–1642 (published 2/12/2004, hereafter Seah).
Due to Applicant' s amendment of the claims, the rejection is modified from the rejection as set forth in the Office action mailed 9/8/2025, as applied to claims 1 & 7-9. Applicant' s arguments filed 1/8/2026 have been fully considered but they are not persuasive.
Claims 12 & 15 are drawn to a method for inverting a chromosomal segment in a crop plant cell comprising introducing a double strand break inducing agent to cut a first and second target site.
Schmidt teaches a method of inducing two double strand breaks about 3kb apart at four loci in the Arabidopsis genome: ADH1, TT4, ECA3, and PSDG (page 578, right column, paragraph 1). This method involved introducing vectors encoding Cas9 and two sgRNA cassettes for specific induction of two double strand breaks into Arabidopsis plants via floral dip and growing the T1 plants; genome targeting and mutations were confirmed with a T7 endonuclease assay and sequencing (page 587, left column, paragraph 3-right column paragraph 4).
Schmidt teaches that some of the plants comprising inversions after transformation and selfing comprised mutations in one or more junctions (page 584, right column, paragraph 4). Mutations in the junctions of the inversions were more common in a mutant that had more frequent microhomology mediated end-joining (page 580, right column, paragraph 2; figure 4).
Schmidt’s method resulted in inversions up to 18kb in length, but natural inversions are much larger and Schmidt envisions using the protocol to induce inversions in the Mbp range (page 585, right column). Schmidt teaches that inversions are major obstacles for breeding as no crossovers can be achieved between inverted regions, for example in introgressing resistance markers into cultivated tomato, while at the same time inversions can stabilize genetic linkages in elite cultivars (page 585 right column & page 578, left column, paragraphs 2-3). Schmidt teaches that it is highly desirable to set up a technology for inducing heritable inversions in plants (page 578, left column, paragraphs 2-3). Mi-1 nematode-resistance is an example of a resistance gene located within an inversion in tomato (page 585, right column).
Schmidt does not teach a working example of the inversion of a chromosomal segment that is 50kbp long.
Seah teaches that the Mi-1 nematode resistance gene in tomato is located in an inverted introgression from L. peruvianum of 650 kbp (abstract, page 1636, left column, paragraph 1).
Before the filing date of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of Schmidt to invert a longer chromosomal segment, such as the 1Mbp range suggested, in a crop plant like tomato. One of ordinary skill would have been motivated to invert a segment of at least 50kb bases in order to revert natural inversions to allow for introgression of favorable alleles like the Mi-1 resistance gene. One of ordinary skill in the art would have had reasonable expectation of success, because natural inversions can be this length, and Schmidt suggests that inducing inversions in the Mbp range is the next step.
Schmidt’s method of Agrobacterium transformation with a construct encoding Cas9 and two specific guide RNAs reads on introducing to a plurality of crop plant cells a double strand break inducing agent capable of site-specifically cleaving first and second target sites. The inversions with resulting indels in the junction sequence read on an inversion heterologous to its chromosome, because the instant specification defines heterologous as having a difference between the original location or composition of polynucleotide and its current location or composition. Additionally, the Mi-1 locus comprises an introgression from another species, L. peruvianum, and so an Mi-1 inversion would read on an inversion heterologous to an L. esculentum chromosome. Infection with Agrobacterium, growing T1 plants comprising the inversion, and confirming the mutation by sequencing reads on incubating under conditions that allow for double strand breakage and repair of the two cleavages, regenerating a crop plant, and validating by genotype of the crop plant.
Regarding claim 15, Schmidt’s suggestion to generate an inversion in “the 1Mbp range” makes obvious generating an inverted chromosomal segment larger than but in the range of 1Mb.
Thus, claims 12 & 15 are obvious over Schmidt and Seah.
Applicant urges that amended claims require “bombarding a plurality of crop plant cells to introduce a Cas endonuclease, a first guide RNA, and a second guide RNA”, which is not taught by Schmidt and Seah (Remarks, page 7, paragraph 4-5).
This argument is unpersuasive to the rejection above, because claims 12 & 15 do not require bombardment.
Applicant urges that Schmidt and Seah do not disclose, teach, or suggest that Agrobacterium tumefaciens-mediated floral dip transformation can achieve inversion of a chromosomal segment comprising at least 50kb of contiguous bases (Remarks, page 7, paragraphs 5-6).
This argument is unpersuasive, because Schmidt teaches that induction of inversions in the Mbp range, which is larger than 50kb, is the next step for testing the inversion protocol. Moreover, Schmidt teaches a motivation to induce inversions of at least 50kbp, because inversion of the Mi-1 gene introgression, which Seah teaches is 650kbp, would enable transfer of resistance to other cultivars. One of ordinary skill in the art would have had reasonable expectation of success, because Schmidt teaches that many natural inversions are much larger. In light of the teachings of Schmidt and Seah, inversion of a chromosomal segment comprising at least 50kb of contiguous bases would have been obvious to one of ordinary skill in the art.
Claim(s) 12-13, 15-16 &38 are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt in view of Bundock et al US 10,995,338 (effective filing date of 12/27/2012, published 12/10/2015, patented 5/4/2021; hereafter Bundock).
Due to Applicant' s amendment of the claims, the rejection is modified from the rejection as set forth in the Office action mailed 9/8/2025, as applied to claims 1, 7-11 & 33. Applicant' s arguments filed 1/8/2026 have been fully considered but they are not persuasive.
Claims 12-13, 15-16 & 38 are drawn to a method for inverting a chromosomal segment in a crop plant cell comprising introducing a double strand break inducing agent to cut a first and second target site.
The teachings of Schmidt are presented above. Schmidt does not teach a working example of the inversion of a chromosomal segment that is 50kbp long or the inverted segment in maize.
Bundock teaches a motivation to break linkage drag in introgression fragments, because all forms of linkage drag slow down and complicate plant breeding (column 4, line 56-column 5 line 3).
Bundock teaches a method of introducing a translocation between chromosomes in a plant cell. Bundock teaches a method of inducing a targeted translocation between B. napus A and C genomes chromosome 8 comprising designing TALENs to bind and cut at two target sites, cloning a nucleotide encoding the TALENs into a plasmid vector and introducing the vector in protoplasts using PEG transfection, then genotyping for targeted translocations using primers specific to the A and C genomes and regenerating calli with targeted translocations (column 29, lines 56-column 30, line 22).
Bundock envisions the method in other species, including maize, sorghum, wheat, soybean, cotton, sunflower, rice, alfalfa, and cucumber (column 9, lines 56-column 10 line 16).
Bundock teaches a method for targeted translocation at chromosome VII in tomato protoplasts comprising introducing a site-specific nuclease, a ZFN, to induce double stranded breaks at a genomic position on both of the homologous chromosomes and detecting translocations using PCR primers (column 20, line 66-column 21, line 32). Bundock teaches that the method comprised designing a plasmid to introduce ZFN targeting two locations at the acetolactate synthase 1 and 2 genes (column 21, lines 45-50). Bundock teaches that this locus is introgressed from wild Solanum pennellii plants which are backcrossed, and F1 seeds are collected (column 21, lines 52-67). Bundock teaches that protoplasts from these plants are transfected with the plasmid (column 22, lines 26-36) then incubated and mixed with alginate and incubated in the dark at 30°C for 7 days (column 22, lines 38-46) before plants are regenerated (column 22, lines 46-62). The genotype of the transformants was validated with PCR and sequencing (column 23, lines 1-37; column 24, lines 20-52).
Bundock teaches a method to break linkage drag at the TYLCV locus to enable translocation or recombination between a 17 MB-long introgressed region from S. chilense and the corresponding S. lycopersicum chromosome comprising a Ty1 and Ty3 locus (column 27, lines 5-58).
Bundock teaches a method for introgressing a chromosomal segment of defined size in tomato to provide a locus responsible for early fruit ripening between markers MM101 and MM107, which are 527 kbp apart (column 27, line 66-column 28 line 2). Bundock teaches a method wherein protoplasts are transformed with constructs for TALENs targeting sequences flanking the loci, and that transformants are analyzed via PCR using chromosome specific primers for validation (column 27 line 66- column 28, line 29). Bundock teaches that tomato lines were crossed to produce an F1 from which protoplasts were created, transfected with TALEN constructs, genotyped for a translocation using PCR primers, and regenerated into plants to self to create an F2 generation (column 28, lines 29-40).
Before the filing date of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of Schmidt to invert a longer chromosomal segment, such as the 1Mbp range suggested by Schmidt or over 10 million contiguous bases as in the TYLCV locus, in a hybrid crop plant like tomato as taught by Bundock. One of ordinary skill would have been motivated to invert a segment of at least 50kb bases in order to revert natural inversions to allow for introgression of favorable alleles or to reduce drag at the TYLCV locus. One of ordinary skill in the art would have had reasonable expectation of success, because natural inversions can be this length, and Schmidt suggests that inducing inversions in the Mbp range is the next step.
Regarding claims 12 & 15, Schmidt’s suggestion to generate an inversion in “the 1Mbp range” makes obvious generating an inverted chromosomal segment larger than but in the range of 1Mb. Inversion that leads to indel mutations and/or inversions of an introgression from a different Lycopersicum species read on an inversion heterologous to its chromosome.
Regarding claims 13, 16 & 38, Bundock teaches the presence of linkage drag at the TYLCV locus, which comprises more than 10 million contiguous bases, envisions the method of chromosomal translocation in maize, and teaches the method in protoplasts, which reads on the inversion performed in a somatic cell.
Claims 12-13, 15-16 & 38 are obvious over Schmidt and Bundock.
Applicant urges that Bundock does not cure the deficiencies in Schmidt because it is unrelated to bombarding crop plant cells to introduce a Cas endonuclease, a first guide RNA, and a second guide RNA, and inverting a chromosomal segment in a crop plant (Remarks, page 7, paragraph 7).
This argument is unpersuasive, because claims 12-13, 15-16 & 38 do not require bombardment. As presented above, it would be obvious to apply the teachings of the method of Bundock, which is a method to break linkage drag comprising making two double strand breaks in a plant chromosome, to the method of Schmidt, which is also taught to be a method to break linkage drag, to arrive at the methods of instant claims 12-13, 15-16 & 38.
Claims 1, 7-11, 31-33 & 36-37 are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt and Bundock as applied to claims 12-13, 15-16 & 38 above, and further in view of Kuluev et al (2019) Russian Journal of Plant Physiology. 66(5): 694–706 (published 8/22/2019, hereafter Kuluev).
Due to Applicant' s amendment of the claims, the rejection is modified from the rejection as set forth in the Office action mailed 9/8/2025, as applied to claims 1, 7-11 & 31-33. Applicant' s arguments filed 1/8/2026 have been fully considered but they are not persuasive.
Claims 1, 7-11 & 33 are drawn to a method for inverting a chromosomal segment in a crop plant cell comprising bombarding a plurality of crop plant cells to introduce a Cas endonuclease to cut a first and second target site. Claims 31-32 & 36-37 are drawn to a method for inverting a chromosomal segment in a crop plant cell wherein a gRNA is provided as an RNA molecule and a Cas endonuclease is provided as a protein.
The teachings of Schmidt and Bundock are presented above and incorporated here. They do not teach the method wherein Cas endonuclease or guide RNA are provided directly to the cell or wherein a Cas endonuclease and guide RNAs are introduced via bombarding a plurality of crop plant cells.
Kuluev teaches a method of transformation of plant cells by biolistic delivery of a ribonucleoprotein (RNP) comprising Cas9 and guide RNA into maize or wheat cells or protoplasts (page 699, left column, paragraph 4 - right column paragraph 2; table 1). Kuluev teaches a motivation for using RNP for biolistic transformation because it improves editing efficiency (page 699, right column, paragraph 2) and does not require the integration of exogenous DNA (page 699, left column paragraph 4) which may allow obtained organisms to be introduced without the regulatory requirements of transgenic plants (page 702, left column, paragraph 3-right column paragraph 1).
Before the time of filing of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of inverting a chromosomal segment taught by Schmidt to substitute introducing a plasmid vector encoding a Cas protein and guide RNA via Agrobacterium transformation with introducing an RNP via biolistic transformation. One of ordinary skill would have been motivated to use an RNP because no foreign DNA would be integrated and introduction would require fewer safety investigations. One of ordinary skill would have had reasonable expectation of success because a wide range of species have been successfully gene edited using RNP. Thus, the method of translocation of a chromosomal segment wherein the Cas endonuclease is provided directly to the cell as a protein (claims 31 & 36) and the guide RNA is provided as an RNA molecule (claims 32 & 37) is obvious in view of Bundock, Schmidt, and Kuluev.
The biolistic delivery of RNP on wheat germs or biolistic bombardment of rice calli with plasmids reads on bombarding a plurality of crop plant cells to introduce a Cas endonuclease and guide RNAs (claim 1). Schmidt teaches a method that reads on the additional steps of claim 1 and suggests using the method in a crop like tomato and to create inversions in the 1 Mbp range. Schmidt’s suggestion to generate an inversion in “the 1Mbp range” makes obvious generating an inverted chromosomal segment larger than but in the range of 1Mb (claim 7).
Regarding claims 8, 9 & 33, Bundock teaches the presence of linkage drag at the TYLCV locus which comprises more than 10 million contiguous bases, comprises resistance loci which reads on QTLs and comprises a favorable allele associated with disease resistance which reads on an agronomic trait. In light of the obviousness of bombardment delivery of CRISPR Cas components taught by Kuluev, claims 8, 9 & 33 are obvious.
Regarding claim 10, Bundock teaches the method of inducing a chromosomal translocation in a hybrid tomato crop to introgress a beneficial trait, and Schmidt teaches that inversions can stabilize genetic linkages in elite cultivars, so it would have been obvious to induce an inversion to stabilize the introgressed trait in a hybrid tomato crop.
Regarding claim 11, Bundock envisions the method of chromosomal translocation in maize, sorghum, wheat, soybean, cotton, sunflower, rice, and alfalfa, making the method in one of these species obvious.
Therefore, claims 1, 7-13, 15-16, 31-33 & 36-38 are obvious over Schmidt, Bundock, and Kuluev.
Applicant urges that Kuluev is unrelated to a method of inverting a chromosomal segment in a plant cell wherein the inverted chromosomal segment comprises at least 50kb of contiguous bases (Remarks, page 7, paragraph 8-page 8, paragraph 1).
This argument is unpersuasive, because the rejection above is based on a combination of references. Applicant is arguing the deficiency of Kuluev in isolation. One of ordinary skill in the art would have found it obvious to use the teachings of Kuluev regarding the delivery of CRISPR/Cas components into plant cells to substitute biolistic bombardment delivery of CRISPR/Cas components for the Agrobacterium-mediated delivery step in the method of Schmidt, because biolistic delivery of components for genome editing was a routine method prior to the filing of the instant application.
Claim(s) 14 is rejected under 35 U.S.C. 103 as being unpatentable over Schmidt and Bundock as applied to claims 12-13, 15-16 & 38 above, and further in view of Verlaan et al (2011) The Plant Journal. 68: 1093–1103 (published 8/26/2011, hereafter Verlaan).
This is a new rejection necessitated by rejoined claim 14.
Claim 14 is drawn to the method wherein the inversion is pericentric.
The teachings of Schmidt and Bundock are presented above. They do not teach an inversion that is pericentric.
Verlaan teaches that the Ty-1 resistance locus to Tomato yellow leaf curl virus, introgressed from Solanum chilense, is generally accompanied by undesired horticultural traits (page 1094, left column, paragraph 4-right column, paragraph 1). Verlaan teaches reducing the introgression size of Ty-1 has been unsuccessful, probably because of suppression of recombination (page 1094, right column, paragraph 2). Verlaan teaches that the severe recombination suppression in the Ty-1 region is the result of chromosomal inversions (page 1095, left column, paragraph 1), including an inversion spanning the centromere (figure 3, page 1096, right column, paragraph 2-page 1098, left column, paragraph 1).
Before the filing of the instant application, it would have been obvious to one of ordinary skill in the art to use the method of Schmidt to invert the pericentric inversion near the Ty-1 resistance locus. One of ordinary skill in the art would have been motivated to invert the introgression in order to overcome the severe recombination suppression caused by the inversion and reduce the linkage drag of undesired horticultural traits. One of ordinary skill in the art would have had reasonable expectation of success, because Bundock taught centromere translocations at this locus in tomato.
Claims 12-16 & 38 are obvious over Schmidt, Bundock, and Verlaan.
Claim(s) 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt and Bundock as applied to claims 12-13, 15-16 & 38 above, and further in view of Boutilier et al (2002) The Plant Cell. 14: 1737–1749 (published 8/1/2002, hereafter Boutilier).
This is a new rejection necessitated by the rejoinder of claims 34-35.
Claims 34-35 are drawn to a method for inverting a chromosomal segment in a crop plant cell comprising providing to the crop plant cell at least one morphogenic factor.
The teachings of Schmidt and Bundock are presented above. They do not teach providing a morphogenic factor to the crop plant cell.
Boutilier teaches a method of in vitro regeneration comprising transforming Arabidopsis plants with a construct encoding the BABY BOOM (BBM) protein (page 1742, left column, paragraph 4). Boutilier teaches that explants expressing transgenic BABY BOOM had faster and more vigorous shoot regeneration than control explants and regenerated into plantlets without added plant growth regulators (page 1743, right column, paragraph 1-2). Boutilier teaches that both Arabidopsis and Brassica formed somatic embryos when transformed with a construct encoding BBM (figure 4).
Before the time of filing of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of inverting a chromosomal segment taught by Schmidt and Bundock to add the method taught by Boutilier comprising transforming plants with a construct for expressing BBM. One would have been motivated to do so because BBM expression led to faster regeneration of plants. One would have had reasonable expectation of success, because the methods of Bundock and Boutilier were both demonstrated to work in Brassica napus and plant transformation methods were routine in the art prior to the filing of the instant application.
Transforming a plant cell with a construct for expressing BBM would be an example of providing the cell with a morphogenic factor (claim 34) wherein the morphogenic factor is BBM (claim 35).
Claims 12-13, 15-16 34-35 & 38 would have been obvious in light of Schmidt, Bundock, and Boutilier.
Claim(s) 29-30 & 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt, Bundock, and Kuluev as applied to claims 1, 7-13, 15-16, 31-33 & 36-38 above, and further in view of Boutilier.
This is a new rejection necessitated by Amendment. Applicant’s arguments filed 1/8/2026 have been considered as they pertain to the current rejection, but they are unpersuasive.
Claims 29-30 & 34-35 are drawn to a method for inverting a chromosomal segment in a crop plant cell comprising providing to the crop plant cell at least one morphogenic factor.
The teachings of Schmidt, Bundock, and Kuluev are presented above. They do not teach providing a morphogenic factor to the crop plant cell.
The teachings of Boutilier are summarized above.
Before the time of filing of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of inverting a chromosomal segment taught by Schmidt, Bundock, and Kuluev, wherein the CRISPR-Cas components are delivered to crop plant cells by biolistics, to add a step taught by Boutilier comprising transforming plants with a construct for expressing BBM. One would have been motivated to do so because BBM expression led to faster regeneration of plants. One would have had reasonable expectation of success, because the methods of Bundock and Boutilier were both performed on Brassica napus and transformation methods in plants were routine prior to the filing date of the instant application.
Transforming a plant cell with a construct for expressing BBM would be an example of providing the cell with a morphogenic factor (claim 29 & 35) wherein the morphogenic factor is BBM (claim 30 & 35).
Claims 1, 7-13, 15-16, & 29-38 would have been obvious in light of Schmidt, Bundock, Kuluev and Boutilier.
Applicant urges that Boutilier is unrelated to a method of inverting a chromosomal segment in a plant cell wherein the inverted chromosomal segment comprises at least 50kb of contiguous bases (Remarks, page 8, paragraph 2).
This argument is unpersuasive, because the rejection above is based on a combination of references. Applicant is arguing the deficiency of Boutilier in isolation. One of ordinary skill in the art would have found it obvious to use the teachings of Boutilier regarding transforming plants with a construct encoding BBM in order to regenerate plants faster after inverting a chromosomal segment, because transformation of plants with morphogenic genes like BBM was a routine method in plant transformation prior to the filing of the instant application.
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, 7, 12, & 29-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-34 of copending Application No. 18/840,944 (reference application, hereafter ‘944). Although the claims at issue are not identical, they are not patentably distinct from each other because the methods encompass steps that are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
‘944 claim 27 is drawn to a method comprising introducing site-specific double strand breaks in at least two distant target sites, wherein the targeted double strand breaks result in a reinversion or a rearrangement of a previously translocated chromosomal segment. ‘944 claim 29 is drawn to the method wherein the inverted chromosome is in a heterologous chromosome. This reads on instant claim 12.
‘944 claim 25 is drawn to a method for paracentric inversion of a chromosomal segment of more than one chromosome in a crop plant cell, comprising introducing to the chromosome a Cas endonuclease and a first and second guide RNA that form a first and second complex and cleave a first and second target site, incubating under conditions that allow for repair of the cleavages resulting in the inversion of the segment, and validating the inversion by genotype or phenotype of the cell or an organism that comprises the cell, wherein the segment comprises at least one million contiguous bases. ‘944 claim 34 is the method wherein the DNA break inducing agent is CRISPR-Cas and is delivered to intact plant cells using particle bombardment.
Although ‘944 claim 25 does not require a step of regenerating a crop plant, validating the inversion in an organism that comprises the cell makes obvious the step of regenerating. Additionally, ‘944 claim 34 specifies delivering the inducing agent to intact plant cells, which reads on bombarding a plurality of crop cells. Thus, instant claim 1 is not patentably distinct from ‘944 claim 34. Instant claim 7, wherein the inverted chromosomal segment is larger than 1Mb is also not patentably distinct.
‘944 claims 30-31 are drawn to the method comprising providing to the crop plant cell at least one morphogenic factor, that is BBM or WUS. ‘944 claim 32 is the method wherein the DNA break inducing agent is CRISPR-Cas and is provided directly to the cell as a protein. ‘944 claim 33 is the method wherein the DNA break inducing agent is CRISPR-Cas and is provided directly to the cell as an RNA molecule.
Instant Claim | Corresponding ‘944 claim
1,7 34
29,30 30,31
31,32 32,33
12 29
Claims 1, 7-9, 11 & 29-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 9, 10, 14, 20, 21, 28, 29, 32, 34 & 37 of copending Application No. 18/713,877 in view of et al (2019) The Plant Journal. 98:577-589 (published 3/22/2019, hereafter Schmidt) and Kuluev et al (2019) Russian Journal of Plant Physiology. 66(5): 694–706 (published 8/22/2019, hereafter Kuluev).
This is a provisional nonstatutory double patenting rejection.
This is a New Rejection
Instant claims 1, 7-9, 11 & 29-32 are drawn to a method for inverting a chromosomal segment in a crop plant cell comprising a first and second genomic target site.
‘877 claim 28 is drawn to a method of engineering chromosomal translocation in a crop plant cell of a large chromosomal segment characterized by at least a first and a second target site (lines 1-3), providing the plant cell with a DNA break-inducing agent designed to bind and cleave the genomic target site, wherein the cell is incubated at a temperature greater than 28°C (lines 3-5), and regenerating a crop plant cell from the plant cell (lines 13-14).
‘877 claim 1 is drawn to a method of chromosomal modification in a crop plant cell comprising providing a DNA break inducing agent to bind and cleave the target site wherein the cell is incubated (lines 9-11), wherein the chromosomal modification is a rearrangement, deletion, duplication, translocation, and/or inversion (lines 20-21). ‘877 claim 2 is further drawn to the method comprising regenerating a crop plant. ‘877 claim 14 is drawn to the method wherein the DNA break inducing agent is a CRISPR-Cas polypeptide.
‘877 claim 5 is drawn to the method wherein the modification is a pericentric inversion and claim 9 is drawn to the method wherein the chromosomal segment comprises at least 50kb of contiguous bases. ‘877 claim 37 is drawn to the method wherein the oligonucleotides are co-delivered with the DNA break inducing agent in the form of RNP complexes or plasmids. ‘877 claims 20 & 21 are drawn to the method comprising providing to the crop plant cell at least one morphogenic factor that is BBM or WUS.
‘877 claims 1, 2 & 14 do not require a first and second genomic target site or a step to validate the translocation in the crop plant cell. ‘877 claim 28 does not require a Cas endonuclease or a step to validate the translocation.
Schmidt teaches a method of inducing two DSB within a single chromosome to obtain inversions by introducing vectors encoding Cas9 and two specific sgRNA cassettes into Arabidopsis plants via floral dip, growing the T1 plants, and confirming the genome targeting with a T7 endonuclease assay and sequencing (page 587, left column, paragraph 3-right column paragraph 4 & page 585, left column paragraph 2). Schmidt’s teaches a method resulting in inversions up to 18kb in length, but natural inversions are much larger and Schmidt envisions using the protocol to induce inversions in the Mbp range (page 585, right column). Schmidt teaches a motivation for the inversions because pre-existing inversions are major obstacles for breeding as no crossovers can be achieved between inverted regions, for example in introgressing resistance markers into cultivated tomato, while at the same time novel inversions can stabilize genetic linkages in elite cultivars (page 585 right column & page 578, left column, paragraphs 2-3).
Before the time of filing of the instant application, it would have been obvious to one of ordinary skill in the art to modify the method of ‘877 claim 28 (lines 1-3) to induce an inversion of at least 50kb contiguous bases and to use a first and second guide RNA to recognize, bind to, and cleave a first and second target site, because two target sites are used in ‘877 claim 28 (lines 1-3) and Schmidt teaches that inversions, including in the Mbp range, are useful for plant breeding to stabilize linkage or reduce linkage drag in introgressed traits. The rationale for combining the two methods would be combining prior art elements according to known methods to yield predictable results.
Before the time of filing of the instant application, it would have been obvious to one of ordinary skill in the art to use a Cas endonuclease and a first and second guide RNA to recognize, bind to, and cleave the first and second target site, because a Cas endonuclease is used as the DNA break inducing agent in co-pending claim 14 as well as in Schmidt. In addition, before the time of filing of the instant application, it would have been obvious to validate the chromosomal inversion by genotyping, as taught by Schmidt. One of ordinary skill in the art would have been motivated to use CRISPR-Cas system delivered via biolistic bombardment as an RNP, in order to avoid alien DNA integration.
Thus, claim 1 is obvious in view of ’877 claim 28 and ‘877 claims 2 & 14 & 37, Schmidt, and Kuluev.
‘877 claim 29 is drawn to the method in maize. ‘877 claim 34 requires the chromosomal segment comprises a QTL. ‘877 claims 4 and 1 are drawn to methods that result in inversion. ‘877 claim 9 is drawn to a chromosomal segment comprising at least 50kb of contiguous bases. ‘877 claim 10 is drawn to the method wherein the chromosomal segment is larger than 1Mb. Use of the method for introgressing an agronomically important trait (instant claim 9), such as disease resistance, would be obvious over Schmidt.
Thus, instant claims 1, 7-9, & 11 are unpatentable over ‘877 claims 1, 2, 4, 9, 10, 14, 20, 21, 28, 29, 32, 34 & 37. See table below for mapping.
Instant Claim | Corresponding ‘877 Claim
1, 9 28, 2, 4, 9, 14, 37
11 29 & 32
8 34 & 32
7 10
29,30 20,21
31,32 37
Conclusion
No claims are allowed.
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/VICTORIA L DELEO/Examiner, Art Unit 1662
/Anne Kubelik/Primary Examiner, Art Unit 1663
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