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 .
Claim Status
Claims 1-19, 25, 27-28 and 30-32 are pending. Claims 20-24, 26, 29 and 33-34 are canceled. Claims 1-19, 25, 27-28 and 30-32 are examined in the instant office action.
All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Amendments
Objections withdrawn from action:
The specification objections are withdrawn. The abstract and specification are amended to address these informalities.
Status of Rejections from action:
The rejection for Claim 13 under 112(b) is withdrawn in view of amendment. Applicant amended to recite "the nucleic acid,".
Claim Rejections - 35 USC § 102(amended)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-19, 25, 28, 30 and 32 REMAIN rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maori et al. (US 20180237790 A1 (previously presented)).
In regards to claims 1 and 5, Maori discloses a method of using cell penetrating peptides to deliver genes into tomato plants with or without cell wall penetrating enzyme (CWDE) (see paragraph [0068] and figure 13). Maori specifically discloses using “KH9-BP100 peptide (SEQ ID NO: 21): dsRNA complexes” (see paragraph [0333], figure 13, and example V). Additionally, Maori discloses on spraying said construct on plants (see paragraph example V [0328]-[0333]), which they confirmed 24 hours post treatment and measure PDS mRNA levels (see figures 15-16).
In regards to claims 2 and 15, Maori discloses spraying said complex on plant tissue including “leaf, a stem, a root, a flower, a fruit, a bud, a shoot, a tuber, a bulb, a seed, an embryo and a seed pod” (see paragraph [0039] and claim 20).
In regards to claims 3-4, Maori discloses the complexes prepared in either water or sodium phosphate buffer and mentions “(i.e. where stability of complexes has been demonstrated and no severe toxic effects were detected)” (see paragraphs [0055]-[0056], figures 8-9, and example V paragraph [0328]).
In regards to claim 6, Maori discloses using cationic cell penetrating peptides such as BP100 (see claim 9 and paragraph [0333]).
In regards to claims 7-9, Maori discloses SEQ ID NO: 21, which has (KH)9 CPP fused with BP100 (KHKHKHKHKHKHKHKHKHKKLFKKILKYL). The (KH)9 sequence has sequence has 100% sequence identity to Applicants SEQ ID NO: 10 (KHKHKHKHKHKHKHKHKH). The BP100 sequence has 100% sequence identity to Applicants SEQ ID NO: 7 (KKLFKKILKYL). Therefore, together SEQ ID NO: 7 & 10 makeup SEQ ID NO: 21 having 100% sequence identity.
In regards to claims 10-14, Maori discloses to enhance transfection adding “enhanced by inclusion of moieties such as proteins or peptides that function for nuclear or other sub-cellular localization, function for transport or trafficking, are receptor ligands, comprise cell-adhesive signals, cell-targeting signals, cell-internalization signals, endocytosis signals, or even cell penetration signals as nucleic acid sequences encoding one or more protein chains.” (see paragraph [0158]). The passage explains that complexes can be improved by adding proteins or peptides, such as CTPs and MTPs, that specifically guide them to the nucleus or other sub-cellular location (e.g. organelles), or facilitate their transport and trafficking within the cell. Furthermore, the Applicant acknowledges that attaching organelle targeting peptides, such as CTPs, to these complexes is a well-established practice in the field (see specification pages 7-8 lines 35-5).
In regards to claim 16, Maori discloses spraying instructions which state that “perpendicular spraying simply means directing the spray directly at the leaf surface at a 90-degree angle” (see paragraph [0311]), which include either adaxial or abaxial side of a plant leaf.
In regards to claims 17-18, Maori discloses modulation gene expression in a plant cell using CPP+dsRNA complex, (see paragraph [0002] and example VI paragraph [0336]). Maori discloses on a method of using cell penetrating peptides to deliver genes into tomato plants with or without cell wall penetrating enzyme (CWDE) (see paragraph [0068] and figure 13). Additionally, Maori discloses that peptide “were dissolved in nuclease free water to a final concentration of 200-1000 mM” (see paragraph [0278]). Maori discloses spraying instructions which state that “perpendicular spraying simply means directing the spray directly at the leaf surface at a 90-degree angle” (see paragraph [0311]), which include either adaxial or abaxial side of a plant leaf.
In regards to claim 19, Maori discloses “to prepare peptide-dsRNA complexes, 1 mM peptide solution is added to dsRNA solution while vortexing in ddH2O or sodium phosphate buffer pH 6.8” (see paragraph [0282]).
In regards to claim 25, Maori defines “Spraying—a way of covering crop foliage with a fluid based medium (i.e. water) mixed with compositions of interest. The method is based on producing high pressure within the tank and release of this pressure through the specialised spray equipment is what assists in covering the total plant foliage with the water and its contents. Spraying can be done from the ground manually with hand held back pack sprayers or with high pressure air-blast spraying equipment either pulled by tractors or self propelled or from the air with aircraft equipped with the necessary equipment to spray fields or orchards from above.” (see paragraph [0190]), all of which can apply said treatment without directly contacting the plant.
In regards to claim 28, Maori discloses that spray application can also include “agrochemical molecule is selected from the group consisting of fertilizers, pesticides, fungicides and antibiotics.” (see claim 35).
In regards to claim 30, Maori discloses “peptide-dsRNA complexes were prepared so that the N/P ratio (ratio of amine groups in the peptide to phosphate groups in the nucleic acid) between the peptide and dsRNA ranges from 0.1-10.” (see paragraph [0281]), which falls in range of 0.5 to 2.0.
In regards to claim 32, Maori discloses “contacting is effected via spraying, dusting, aerosol application or particle bombardment” (see claim 13), which particle bombardment is considered a method of transfection.
Accordingly, the claimed invention is anticipated by the prior art.
Response to Arguments
Since the rejections have been modified to reflect the amendment to the claims, only the arguments that are relevant to the current rejections are addressed.
Applicant is arguing that the prior art discloses using cell wall degrading enzymes, while the instant application does not contain a cell wall degrading enzyme. (Remarks, October 10, 2025, page 7).
This argument has been fully considered but is not found persuasive.
MPEP states “A claim is anticipated only if each and every element as set forth in the claim is found, either expressly or inherently described, in a single prior art reference." Verdegaal Bros. v. Union Oil Co. of California, 814 F.2d 628, 631, 2 USPQ2d 1051, 1053 (Fed. Cir. 1987)., (see section 2131).
Applicant is reminded that this is a 102 rejection and not a 103 rejection. The Office agrees that Maori does in fact use cell wall degrading enzyme. However, a fuller reading of Maori also discloses using a cell penetrating peptide without the use of a cell wall degrading enzyme (CWDE), (see image below).
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Maori discloses introducing a nucleic acid (i.e. dsRNA) into a plant, (i.e. tomato plant), by spraying said construct on plants, (see paragraph example V [0328]-[0333]), which they confirmed 24 hours post treatment and measure PDS mRNA levels, (see figures 15-16). Therefore, since Maori discloses every element of the claimed invention the claims are anticipated.
At least for these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 103(amended)
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 27 REMAINS rejected under 35 U.S.C. 103 as being unpatentable over Maori et al., (US 20180237790 A1 (previously presented)) as applied to claim 1, and further in view of Dalakouras et al., (Genetically Modified Organism-Free RNA Interference: Exogenous Application of RNA Molecules in Plants, 2019 Plant Physiology, Volume 182, Issue 1, January 2020, Pages 38–50(previously presented))
a. Regarding claim 27, Maori teaches a method of using cell penetrating peptides to deliver genes into tomato plants with or without cell wall penetrating enzyme (CWDE) (see paragraph [0068] and figure 13). Maori specifically discloses using “KH9-BP100 peptide (SEQ ID NO: 21): dsRNA complexes” (see paragraph [0333], figure 13, and example V). Additionally, Maori teaches on spraying said construct on plants (see paragraph example V [0328]-[0333]), which they confirmed 24 hours post treatment and measure PDS mRNA levels (see figures 15-16).
b. Regarding claim 27, Maori does not specifically teach multiple treatment applications.
c. Regarding claim 27, Dalakouras teaches that “A major issue concerning the aforementioned approaches is that dsRNA application offers a short antiviral protection window (usually 5–10 d), because dsRNA eventually is degraded. Thus, dsRNA would need to be supplied afresh in frequent intervals for lifelong crop protection.”, (see page 43 last paragraph).
d. Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Maori by using repeated/consecutive applications of additional solution, for example, as taught by Dalakouras.
One would be motivated to do so because it would ensure that solution as applied by Maori would provide increased protection as it is known that applications last for short periods of time.
One would have a reasonable expectation of success in doing so because Dalakouras teaches dsRNA treatments would need to be supplied in frequent intervals for lifelong crop protection.
Response to Arguments
Applicant is arguing that “Maori does not teach or suggest every claim element. Dalakouras … [does] not remedy the deficiencies of Maori and, at best, are cited as allegedly disclosing subject matter in dependent claims” (see page 8). The argument is not persuasive because as noted above Maori does, in fact, teach compositions in which a cell wall degrading enzyme is not used. The rejection is maintained.
Claim 31 REMAINS rejected under 35 U.S.C. 103 as being unpatentable over Maori et al., (US 20180237790 A1 (previously presented)) as applied to claim 1, and further in view of Numata et al., (WO 2017126604 A1 (previously presented)).
a. Regarding claim 31, Maori teacehs a method of using cell penetrating peptides to deliver genes into tomato plants with or without cell wall penetrating enzyme (CWDE) (see paragraph [0068] and figure 13). Maori specifically teaches using “KH9-BP100 peptide (SEQ ID NO: 21): dsRNA complexes” (see paragraph [0333], figure 13, and example V). Additionally, Maori teaches on spraying said construct on plants (see paragraph example V [0328]-[0333]), which they confirmed 24 hours post treatment and measure PDS mRNA levels (see figures 15-16).
b. In regards to claim 31, Maori does not specifically teach on the nucleic acid being a CRIPSR-Cas guide RNA.
c. Regarding claim 31, Numata teaches “In the present invention, when the target protein to be introduced into the target plant cell is Cas 9, it is preferable that the complex of the present invention further comprises gRNA in order to allow simultaneous delivery of Cas 9 and gRNA. The gRNA can be bound to the complex, for example by ionic interaction with the carrier peptide.”, (see page 5 first paragraph, and claims 1 and 9). Specifically, Numata teaches using CRIPSR-Cas9 guide RNA complexed together with a peptide which includes BP100 (KKLFKKILKYL), (see page 2 top paragraph 15 middle section of last paragraph, and claims 1 and 9).
d. Therefore, prior to the effective filing date of the instant invention it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Maori by incorporating the CRISPR -Cas9 editing systems, as taught by Numata.
One would be motivated to do so because it would ensure that the delivery of dsRNA complexes as applied by Maori are precisely targeted and integrated for stable gene expression as it is known that CRISPR effectively delivers the genetic material.
One would have a reasonable expectation of success in doing so because Numata teaches a proven road map of using CRISPR Cas 9 delivery systems coupled with CPP’s would efficiently and effectively deliver desired genetic material via spraying.
Response to Arguments
Applicant is arguing that “Maori does not teach or suggest every claim element. … Numata [does] not remedy the deficiencies of Maori and, at best, are cited as allegedly disclosing subject matter in dependent claims” (see page 8). The argument is not persuasive because as noted above Maori does, in fact, teach compositions in which a cell wall degrading enzyme is not used. The rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662