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 .
Information Disclosure Statement
The Information Disclosure Statements filed on 5/16/2025, 11/14/2025, 3/25/2026 have been entered and considered. Initialed copies of the form PTO-1449 are enclosed with this action.
Status of claims
On 7/9/2025, claim set was amended, canceling many claims.
Claims 1, 3-4, 12-13, 17-18, 23, 25-26, 39-40, 47-50, 60-62, 65 are pending and examined in the office action.
Priority
Instant application 19210545, filed 05/16/2025, is a Continuation of 17045747, filed 10/06/2020, now U.S. Patent 12331329.
17045747 is a National Stage entry of PCT/US2019/033984, International Filing Date: 05/24/2019.
PCT/US2019/033984 Claims Priority from Provisional Application 62676228, filed 05/24/2018.
62676228 disclosed the claimed subject matter. Thus, the priority is recognized.
Interpretation of "dry mature plant embryo explant"
The specification does not define "dry mature plant embryo explant".
According to specification ([0022]), "A "dry excised explant" is a mature embryo explant taken or excised from a mature dry seed. A plant seed naturally dries during its maturation process. As described further below, other types of explants may be taken or excised from a mature seed depending on their treatment, such as after wetting, imbibing, etc., a dry seed, and an explant may be wetted, imbibed, etc., after being excised from a dry seed.
The specific also does not provide any example of “delivering to a dry mature plant embryo explant via bacterially mediated transformation a recombinant DNA construct”. Examples 1-5, 7 are examples of particle bombardment. Example 6 is an example of identification.
A seed comprises an embryo.
Accordingly, a "dry mature plant embryo explant" is a mature embryo explant taken or excised from a mature dry seed. After being wetted, imbibed, etc., such explant still reads on a "dry mature plant embryo explant".
Otherwise, the claims may have an enablement issue.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 1, 3-4, 12-13, 17-18, 23, 25-26, 39-40, 47-50, 60-61 are rejected under 35 U.S.C. 103 as being unpatentable over Shultz et al (WO 2018085693, published 5/11/2018, filed 11/3/2017, priority 11/4/2016 to US62418078), in view of Li et al (Optimization of Agrobacterium-Mediated Transformation in Soybean. Frontiers in Plant Science. P1-15, 2017).
Claim 1 is drawn to a method comprising:
a) delivering to a dry mature plant embryo explant via bacterially mediated transformation a recombinant DNA construct comprising a sequence encoding a site-specific nuclease, wherein the sequence is operably linked to a plant-expressible promoter; and
b) regenerating a plant from the dry mature plant embryo explant, wherein the regenerated plant comprises an edit or site-directed integration at or near the target site of the site- specific nuclease in the genome of at least one cell of the regenerated plant,
for editing a genome of a plant (preamble).
Claim 3 limits the transformation to Agrobacterium mediated transformation.
Claim 17 limits the site specific nuclease to Cas9 and so on.
Regarding claims 1, 3, 17
Shultz et al teach a method of altering/editing a genome of a plant comprising:
delivering construct comprising DNA encoding RNA-guide site-specific nuclease (Cas9) into plant (nicotiana benthamiana and maize) seeds comprising embryo (Examples 4-6, [00103]-[00122]).
Dry mature seeds were suspended (thus are removed from the plant) and wetted in MS culture medium before transformation ([00107]), reading on explant. The cultured and wetted seed reads on dry mature plant embryo explant.
The constructs comprise plant expressible promoter (PcUbi4-2, Example 4, table 5, [00105]).
After the transformation, the seeds comprising genomic modification is growing and producing progeny, thus, the explants were regenerated to a plant. The plant and progeny were tested for gene modification using phenotype and/or molecular assay. The seed, plant and progeny comprise editing and gene integration (each of the Examples 4-6, [00111], [00115], [00121]).
Thus, Shultz et al teach and demonstrated all of the limitations of claims 1-2,
except
do not explicitly teach via bacterially mediated transformation to delivery the recombinant construct (Examples 4-6 are not using bacterially mediated transformation, thus, a 102 rejection is not made).
Shultz et al nevertheless suggest that Agrobacterium mediated transformation is a routine technique and is an embodiment of the invention including using Agrobacterium mediated transformation to deliver CRISPR-Cas nucleases ([0020], [0023], [0025], [0035]). Shultz et al also cite references teaching Agrobacterium mediated transformation ([0020]).
Nevertheless, Li et al teach a detailed method of transforming soybean by Agrobacterium mediated transformation (Title, Abstract, whole article).
Specifically, Li et al teach imbibing mature and dry soybean seeds (reading on dry mature plant embryo explant), and culturing the imbibed seeds with Agrobacteria (p4, left col, last para, right col, 1st to 2nd paras).
Li et al demonstrated that the transformation was successful, and transgenic plants were regenerated from the infected seeds (p4, fig 2, J and K, Results in p6-11).
Li et al teach that Agrobacteria and particle bombardment are functional equivalent in plant transformation, and that about 85% of the transgenic plants are obtained using the Agrobacterium-mediated transformation method (p2, left col, 2nd and 3rd para).
Hence, the only difference between Shultz et al and Li et al is a nuclease vs another DNA molecule of interest.
Regarding dependent claims
Shultz et al teach that particle bombardment, as Agrobacterium-mediated method, are used for transformation and gene editing ([0027]), and teach the detailed method of gene editing by bombardment (Example 7, [0123]-[0133]), the limitation of claim 3.
Shultz et al teach that the transformation used a construct comprising T-DNA (Same Example 4, [00104], claim 8), the limitation of claim 4.
Shultz et al teach that the gene of interest/insertion/transgene and the nuclease are in the same construct (example 4, [00104], table 5), thus, the edit or site-specific integration is near the site of nuclease, the limitation of claim 12.
As analyzed above, after the transformation, the plant and progeny were tested for gene modification using phenotype and/or molecular assay. The seed, plant and progeny comprise editing and gene integration (Example 4, [00103], [00111]). Thus, Shultz et al teach the limitation of claim 13.
Shultz et al suggest Cpf1, like Case9, is a Cas endonuclease, and can be transformed to the dry mature plant embryo explant ([0012], [0015], [0017], claim 18), the limitation of claim 18.
Shultz et al teach that guide-RNA and terminators and the nuclease are in the same construct (example 4, [00104], table 5). Claim 1 only requires nuclease. The guide RNA or terminator is a second recombinant DNA molecule. Thus, Shultz et al teach the limitation of claim 23.
Regarding claims 25-26, 48-50, according to specification ([0083]), a “donor molecule”, “donor template”, or “donor template molecule” (collectively a “donor template”), which may be a recombinant polynucleotide, DNA or RNA donor template or sequence, is defined as a nucleic acid molecule having a homologous nucleic acid template or sequence (e.g., homology sequence) and/or an insertion sequence for site-directed, targeted insertion or recombination into the genome of a plant cell via repair of a nick or double-stranded DNA break in the genome of a plant cell. Shultz et al teach that the construct comprises multiple insertions including gene of interest (encoding aminoglycoside adenylyltransferase sequences for selection, reading on transgene and marker gene) and promoter (Example 4, [00104]-[0105], table 5). The construct comprises CRISPR-Cas ([00105]) and transgene, which produces site-specific genome modification by homologous recombination ([0028]). Accordingly, Shultz et al teach second DNA molecule (the first is nuclease) being donor molecule along with the nuclease encoding molecule, the molecule being an insertion, a transgene/marker gene, teaching the limitations of claims 25-26, and 48-50.
Regarding claims 39-40, 47, the specification uses “construct” and “vector” interchangeably ([0101]). Schultz et al teach delivering a second DNA molecule thus teach claim 23, but do not teach delivering a second DNA construct comprising guide RNA in Example 4 above. Schultz et al, however, teach that guide RNA expressed from one vector/construct, and the RNA guided nuclease from a second vector. Schultz et al also teach using different vectors/constructs for expressing different guide RNAs ([0021]). Schultz et al actually made different vectors to express nuclease and guide RNA (sgRNA) (Example 8, [00135]). Thus, Shultz et al at least suggest the limitation of claims 39-40, 47.
Nicotiana benthamiana above in Example 4 is a dicot, thus, the Shultz et al teach the limitation of claim 60.
Shultz et al applying the method to soybean ([0039]) and the method of editing gene of soybean (Example 1, [0073]), the limitation of claim 61.
An invention would have been obvious to one ordinary skill in the art if any teaching, suggestion or motivation in prior art leading the one to combine the teaching(s) or suggestion(s) of the cited references to arrive the claimed invention.
It would have been obvious for one ordinary skill in the art to modify the invention of Shultz et al, such that the method uses Agrobacterium mediated transformation to deliver the site-specific nuclease Cas9, as strongly suggested by Shultz et al, and explicitly taught and demonstrated by Li et al. One ordinary skill in the art would have been motivated to do so, because Agrobacterium mediated transformation is a functional alternative of other transformation methods and demonstrated in detail by Li et al. The expectation of success would have been high, because both Shultz et al and Li et al used the same imbibed dry mature plant embryo explant, the only difference between Shultz et al and Li et al is a nuclease vs another DNA molecule of interest, and the Agrobacterium mediated transformation is a routine method producing 85% of transgenic plants.
In addition, the specification does not provide any example of “delivering to a dry mature plant embryo explant via bacterially mediated transformation a recombinant DNA construct”. Thus, the applicant merely claims what the prior art taught or/and suggested.
Therefore, the invention would have been obvious to one ordinary skill in the art.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Shultz et al in view of Li et al, as applied to claim 1 above, and further in view of Liang et al (Selection of highly efficient sgRNAs for CRISPR/Cas9-based plant genome editing. Nature Scientific Reports, 1-8, 2016).
Claim 1 has been analyzed above.
Claim 62 limits claim 1, wherein the mature embryo explant comprises, prior to the delivering step, a guide RNA (gRNA).
As analyzed above, Schultz et al teach that the guide RNA and the DNA encoding the site-specific nuclease are in different vectors. But, Schultz et al do not teach delivering DNA encoding site-specific nuclease to plant cells comprising guide RNA (prior to delivery).
Liang et al teach that some guide RNAs comprised in plant cell could lead to off-target editing by CRISPR-Cas (not at intended site, thus not desirable), and teach locating (intended and unintended) guide RNAs (sgRNA) in plant cells for next testing (p4, 2nd para).
Liang et al continue to teach the next testing is to deliver Cas-sgRNA (Cas is a site-specific nuclease) to the plant cells comprising the (intended and unintended) guide RNAs, for selecting guide-RNAs leading to predicted/intended target sites (p4, last para; p5, 1st para).
Liang et al further teach the advantage of such tests is reducing off-targeting and increasing editing accuracy (p4, 2nd para; p6, 1st para).
It would have been obvious for one ordinary skill in the art to modify the invention of Shultz et al, such that the method further comprises delivering Cas-sgRNA (Cas is a site-specific nuclease) to the plant cells comprising guide RNA, as suggested by Shultz et al and explicitly taught by Liang et al. One ordinary skill in the art would have been motivated to do so, because of the advantage of testing guide-RNAs and selecting that are specific to the intended editing from plant cells as taught and demonstrated by Liang et al. The expectation would have been high, because the method steps of Schultz et al and Liang et al are essentially the same and routine, only difference is the target plant cells comprise guide RNAs. Off-target testing is also routine as taught by Liang et al.
Therefore, the dependent claim would have been obvious to one ordinary skill in the art.
Claim 65 is rejected under 35 U.S.C. 103 as being unpatentable over Shultz et al in view of Li et al, as applied to claim 1 above, and further in view of Patnaik et al (Agrobacterium-mediated transformation of mature embryos of Triticum aestivum and Triticum durum. Current Science. 91, 307-317, 2006) viewed with evidence from Tri-States (Dry-Grain Management Means Longer Storage Times for Wheat, 8/20/2018).
Claim 1 has been analyzed above.
Claim 62 limits claim 1, wherein the dry mature embryo explant has a moisture content within a range from about 3% to about 25% or wherein the dry mature embryo explant is excised from a plant seed having a moisture content within a range from about 3% to about 25%.
Shultz et al in view of Li et al are silent on such specific limitation.
Patnaik et al teach excising an explant from dry mature (wheat) plant seed, (307, right col, last para, p308, left col, 1st para), and used the explant for transformation (p308, right col, 1st para) and demonstrated success by PCR and protein assay (p309, whole page).
Tri-States provides evidence that the ideal wheat moisture content at harvest is between 18% and 20%. This is above the ideal wheat moisture content for stored wheat. You’ll want to bring the moisture content down to 13.5% if you plan to sell soon, since that is the ideal wheat moisture content for the best-selling price. If you plan to store the wheat for a year, or more, you’ll want to bring it down even more to 12.5%.
Thus, the mature wheat seed of Patnaik et al reads on “the mature embryo explant is excised from a plant seed having a moisture content within a range from about 3% to about 25%”, the limitation of claim 65.
It would have been obvious for one ordinary skill in the art to modify the invention of Shultz et al in view of Li et al, when wheat is the plant, such that the mature embryo explant is excised from a plant seed having a moisture content within a range from about 3% to about 25%, silent by Shultz et al or Li et al, but taught by Patnaik et al viewed with evidence from Tri-States. One ordinary skill in the art would have been motivated to do so, because the moisture content would have been ideal as evidenced from Tri-States. The expectation would have been high, because the optimal moisture content would only improve the method of Shultz et al in view of Li et al.
Therefore, the dependent claim would have been obvious to one ordinary skill in the art.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Instant and reference applications share inventors and the same applicant Monsanto. 2 rejections are made:
Claims 1, 3-4, 12-13, 17-18, 23, 25-26, 39-40, 47-50, 60-62, 65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-8, 13, 19, 21, 23-24, 29, 34-41, 44 of co-pending Application 19360252 (USPGPUB 20260043038).
The co-pending applicant claims (amended 12/3/2025):
Claim 1. “A method of editing a genome of a plant, comprising:
a) excising an embryo from a dry mature plant seeds, thereby producing a dry-excised mature plant embryo explant;
b) delivering to the dry-excised mature plant embryo explant a particle coated or applied with a site-specific nuclease, wherein the site-specific nuclease is a CRISPR associated protein, wherein the CRISPR associated protein is comprised in a ribonucleoprotein that further comprises a guide RNA- or a nucleic acid encoding the site specific nuclease; and
c) regenerating a plant from the dry-excised mature plant embryo explant without forming an embryogenic callus or callus culture from the dry-excised mature plant embryo explant, wherein the regenerated plant comprises an edit or site-directed integration at or near the target site of the site-specific nuclease in the genome of at least one cell of the regenerated plant”.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Reference claim 1 teach instant claims 1, 3 in a more specific way, including a specific nuclease CRISPR associated protein and ribonuclease, and callus, except do not claim
“dry mature plant embryo explant” and
“bacterially mediated transformation”.
The "dry mature plant embryo explant" is interpreted above.
As analyzed above, in view of Shultz et al and Li et al, delivering DNA encoding site-specific nuclease into a “dry mature plant embryo explant” of a plant via “bacterially mediated transformation” is deemed obvious. Li et al also teach that particle bombardment and Agrobacterial mediated transformation are functional equivalent.
Regarding dependent claims, reference claim 13 teaches the limitation of instant claims 17-18.
Reference claim 41 teaches the limitation of instant claim 62.
Reference claim 44 teaches the limitation of instant claim 65.
Reference claims 7-8, 19, 21, 23-24, 29, 34-40 teach or suggest the limitations of instant claims 4, 12-13, 23, 25-26, 39-40, 47-50, 60-61.
In addition, as analyzed above, the dependent claims are also deemed obvious in view of Shultz et al and Li et al.
Therefore, the instant claims and reference claims are obvious over each other.
Claims 1, 3-4, 12-13, 17-18, 23, 25-26, 39-40, 47-50, 60-62, 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 7-11, 13-25 of US Patent 12331329.
The USP claims:
Claim 1. “A method of editing a genome of a plant, comprising:
a) excising an embryo from a dry mature plant seed, thereby producing a dry-excised mature plant embryo explant;
b) delivering to the dry-excised mature plant embryo explant via particle bombardment a recombinant DNA construct comprising a sequence encoding a site-specific nuclease, wherein
i) the site-specific nuclease is a ribonucleoprotein;
ii) the site-specific nuclease is Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Csn1, Csx12, Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx15, Csf1, Csf2, Csf3, Csf4, Cpf1, CasX, CasY, CasZ, an Argonaute protein, or a homolog or modified version thereof;
iii) the site-specific nuclease is not a guided nuclease; or
iv) the site-specific nuclease is a meganuclease, a zinc-finger nuclease (ZFN), a recombinase, a transposase, or a transcription activator-like effector nuclease (TALEN), and
wherein the sequence encoding the site-specific nuclease is operably linked to a plant-expressible promoter,
c) culturing the dry-excised mature plant embryo explant after bombardment for at least two days in dark at about 37° C.; and
d) regenerating a plant from the dry-excised mature plant embryo explant without forming an embryogenic callus or callus culture from the dry-excised mature plant embryo explant,
wherein the regenerated plant comprises an edit or site-directed integration at or near the target site of the site-specific nuclease in the genome of at least one cell of the regenerated plant.”
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Reference claim 1 teach instant claims 1, 3, 17 and 18 in a more specific way, including a specific condition of culturing the dry-excised mature plant embryo explant at least two days in dark at about 37° C, except do not claim
“dry mature plant embryo explant” and
“bacterially mediated transformation”.
The instant "dry mature plant embryo explant" is interpreted above.
As analyzed above, in view of Shultz et al and Li et al, delivering DNA encoding site-specific nuclease into a “dry mature plant embryo explant” of a plant via “bacterially mediated transformation” is deemed obvious. Li et al also teach that particle bombardment and Agrobacterial mediated transformation are functional equivalent.
Regarding dependent claims, reference claims 3-5, 7-11, 13-22, 25 teach or suggest the limitations of instant claims 4, 12-13, 23, 25-26, 39-40, 47-50, 60-61.
Reference claim 23 teaches the limitation of instant claim 62.
Reference claim 24 teaches the limitation of instant claim 65.
In addition, as analyzed above, the dependent claims are also deemed obvious in view of Shultz et al and Li et al.
Therefore, the instant claims and reference claims are obvious over each other.
Conclusion
No claim is allowed.
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/Wayne Zhong/
Primary Examiner, Art Unit 1662
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