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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/27/2026 has been entered.
Claim Status
Claims 1-19, 25, 28 and 30-32 are pending. Claims 20-24, 26, 27, 29 and 33-34 are canceled. Claims 1-19, 25, 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All previous rejections not set forth below have been withdrawn.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
Status of Rejections from action:
The rejection for Claims 1-19, 25, 28, 30 and 32 under 102 is withdrawn in view of amendment. Applicant amended to recite "applying additional solution after step b) by spraying".
In regard to Claims 1-9, 11-18, 25 and 30-32 a rejection under 103 is added.
In regard to Claims 1, 10, 17, 19 and 28 a rejection under 103 is added.
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.
Claim 32 is 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 32 recites the limitation “the complex”: there is insufficient antecedent basis for this limitation as the claim from which claim 32 depends is not directed to a “complex” but rather a nucleic acid “complexed” or joined to a cell penetrating peptide.
Moreover, the specification fails to disclose the method where the complex is applied to a plant concurrently with “another” transfection method is unclear. Therefore, the metes and bounds of the claim are indefinite because it is not clear what in addition to the “complex” is concurrently transfected into the plant, and the purpose of concurrently applying another transfection method to the plant while also applying the claimed “complex” is unclear.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-9, 11-18, 25 and 30-32 are NOW rejected under 35 U.S.C. 103 as being unpatentable over Numata et al. “Local gene silencing in plants via synthetic dsRNA and carrier peptide”, 2014, Plant biotechnology journal vol. 12,8: 1027-34.(U) in view of Dalakouras et al. “Induction of Silencing in Plants by High-Pressure Spraying of In vitro-Synthesized Small RNAs”, 2016, Front. Plant Sci. 7:1327(V), 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)).
In regard to claims 1-9,15-18, 25 and 30, Numata et al. teach applying a solution of “(KH)9-Bp100 peptide (amino acid sequence: KHKHKHKHKHKHKHKHKHKKLFKKILKYL) as a dsRNA carrier, dsRNA–peptide complexes prepared at different molar ratios (peptide/dsRNA ratio: 0.5, 1, 5, 10, and 20)” (pg. 1027 col.2 and fig.1) … “in RNase-free water” (pg.1032 col.2) to plant leaf/cell “for the down-regulation of target gene expression” (fig.1), which do not comprise cell wall degrading enzyme or any other additives. Numata et al.’s (KH)9-Bp100 peptide comprises both SEQ ID NO: 7 and SEQ ID NO: 10 and having 100% sequence identity.
In regard to claims 11-14, claim 14 recites that cell penetrating peptide (CPP) has the function of an organelle targeting peptide. Therefore, because Numata et al. teach a CPP it necessarily follows that this CPP acts as organelle targeting peptide that can localize into subcellular compartments.
In regard to claims 1-9,15-18, 25 and 30-32, Numata et al. does not teach spraying a solution or applying multiple treatments of said spray solution, does not teach applying said solution concurrently with another transfection method, and does not teach utilizing CRISPR.
In regard to claims 1-9,15-18, 25 and 30, Dalakouras et al. (2016) teach high pressure spraying to deliver dsRNA’s (Abstract), specifically stating that “The method itself is not damaging siRNAs. We provide a time-saving and cost-efficient procedure for the introduction of siRNAs which opens the perspective to easily identify molecules efficiently initiating silencing by high-throughput screens” (pg. 4 col.2).
In regard to claims 1-9,15-18, 25 and 30, Dalakouras et al. (2019) teach that “Conjugating RNA molecules to nanoparticles and carrier peptides greatly enhances their resistance to nucleases and efficiency of delivery” and “when Arabidopsis leaves were infiltrated with 21-nt sRNAs fused to a positively charged carrier peptide that combined a copolymer of His and Lys, (KH)9 (18 amino acids)” (pg. 38 col.2).
Dalakouras et al. (2019) teach 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).
In regard to claim 31, Dalakouras et al. (2019) teach motivation for using CRISPR in conjunction with dsRNA’s (pgs. 46-47 last sentence).
In regard to claim 32, Dalakouras et al. (2019) teach different transfection methods “High pressure spraying allows the symplastic delivery of exogenous RNA whereas petiole absorption and/or trunk injection results in apoplastic delivery of the exogenous RNA” (pg. 38 col.2 and fig.2).
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 Numata et al. by instead spraying the CPP+dsRNA repeatedly, for example as taught by Dalakouras et al. (2016) and Dalakouras et al. (2019) because it is a design choice: spraying as opposed to application by a syringe leads to the predictable introduction of dsRNA in the plant cell in a time-saving and cost-efficient procedure.
In this way, one would ensure that the solution of Numata et al. would remain functional and in the plant cell as it is known that application of dsRNA lasts for short periods of time (e.g., see Dalakouras 2019).
One would have a reasonable expectation of success in doing so because each of Numata et al. and Dalakrouas et al. teach the successful introduction of inhibitory RNA molecules in the plant cell.
One would have found it obvious, and with a reasonable expectation of success, to modify the teachings of Numata et al. by instead using a CRISPR-cas guide RNA because it is also a design choice that is specifically suggested by Dalakouras et al. and is a known methodology in the art (e.g., see p. 47, col. 2). Namely, both dsRNA technology and the use of CRISPR technology lead to the predictable inhibition of a target gene of interest.
One would be motivated to utilize different transfection methods because Dalakouras et al. (2019) teach the benefits of one over the other, so one would have a high reason expectation of success since Dalakouras et al. (2019) successfully delivered said complexes.
Claims 1, 10, 17, 19 and 28 are NOW rejected under 35 U.S.C. 103 as being unpatentable over Numata et al. “Local gene silencing in plants via synthetic dsRNA and carrier peptide”, 2014, Plant biotechnology journal vol. 12,8: 1027-34.(U) in view of Dalakouras et al. “Induction of Silencing in Plants by High-Pressure Spraying of In vitro-Synthesized Small RNAs”, 2016, Front. Plant Sci. 7:1327(V), 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)) as applied to claims 1 and 17 and further in view of Maori et al. (US 20180237790 A1 (previously presented)).
The teachings of Numata et al., Dalakouras et al. (2016) and Dalakouras et al. (2019) as applied to claims 1 and 17 are addressed above.
In regard to claims 10, 19 and 28, Numata et al., Dalakouras et al. (2016) and Dalakouras et al. (2019) do not teach further adding an organelle targeting peptide, supplementing solution with salt/or a buffer, a method of selectively controlling the growth of weeds and the solution further comprising a herbicide or other pesticide.
In regards to claim 10, Maori et al. teach 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 regard to claim 19, Maori et al. teach CPP+dsRNA 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]). Maori et al. teach “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 regard to claim 28, Maori et al. teach to “include additional plant-beneficial or agrochemically active compounds” (para. [0250]) to the spray application such as “agrochemical molecule is selected from the group consisting of fertilizers, pesticides, fungicides and antibiotics.” (see claim 35).
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 Numata et al., Dalakouras et al. (2016) and Dalakouras et al. (2019) by including salt and/or a buffer in the water solution comprising the CPP because Maori specifically teaches and suggests making this solution. One would have a reasonable expectation of success in doing so because each of Numata et al. and Dalakouras et al. (2016) teach the successful application of inhibitory RNA in various solutions.
Furthermore, one would be motivated to improve the complexes by adding a organelle targeting proteins to successfully guide to specific organelles or subcellular location, because it is well established practice in the field as taught by Maori et al.
Moreover, one skilled in the would be motivated to include pesticides as it is a well-established practice to successfully include a beneficial agrochemical in the complex (claim 35 and para. [0250]) as taught by Maori et al.
Conclusion
No claims are allowed.
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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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