DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 10-19, in the reply filed on 2/4/2026 is acknowledged.
In response to the species election, applicant elected (i) the peptide of SEQ ID NO: 1, (ii) a double-stranded RNA molecule, and (iii) non-covalent bond shown as follows. The Genus S is applied to election of a covalent bond as specified in the restriction requirement at page 5 dated 12/19/2025.
Claim 11 requires fusion the RNA to a cell-penetrating peptide, which is a covalently binding not reading on the elected non-covalent bond. In addition, the specification defines a double-stranded RNA (dsRNA) is defined as a small entity of the double-stranded RNA corresponding with (part of) the target gene [00133]. The dsRNA is processed within the cell into fragments that direct RNAi [00135]. Double-stranded RNA targeting one or more genes for knockdown of transcripts and/or proteins in cells [00230], which does not comprise a coding sequence for translation to a protein. Therefore claims 14-18 directed to a coding sequence is further withdrawn for not reading on the elected double-stranded RNA species.
Claims 11 and 14-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 2/4/2026.
Response to Argument
Applicant’s argument of species election that the genus R, B, and S may be found in a single field of search with minimal burden of search is not persuasive. This species election is under PCT-371 application, but the rules of 35 USC 121 are not applied to PCT-371 application. Furthermore, applicant did not provide sufficient evidence to show a reference found in a single field of search comprises all the limitations under species election to support the argument.
Thus, the species election is maintained.
Claim Status
Claims 1-19 are pending.
Claims 20-60 are cancelled.
Claims 1-9 are withdrawn as being directed to a non-elected invention. Claims 11 and 14-18 are further withdrawn as directed to a non-elected species, the species election having been made with traverse on 2/4/2026.
Claims 10, 12-13, and 19 have been examined.
Priority
This application is a 371 of PCT/US21/62321 12/08/2021
PCT/US21/62321 has PRO 63/126,087 12/16/2020
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6/13/2023, 1/2/2025, and 9/15/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 10 and 12 are objected to because of the following informalities:
Claim 10 contains the acronym “RNA”, and an acronym in the first instance of claims should be expanded upon/spelled out as “ribonucleic acid” with the acronym indicated in parentheses as (RNA). The abbreviations can be used thereafter.
Claim 12 is objected to the phrase “insect cell is selected from the group of…”. The phrase should be revised to “insect cell is selected from the group consisting of…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 19 is drawn to “contacting is performed ex vivo, in vivo, or in vitro” including every possible way to contact. Thus, the limitations of claim 19 fail to further limit the contact of step c in claim 10. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
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.
1. Claims 10, 12, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Siaussat et al. (Cell. Mol. Life Sci. 64 (2007) 365 – 376) in view of Tomich et al. (WO 2020/198020 A1, cited in IDS).
Claim 10 is drawn to a method of introducing a molecule into an insect cell comprising
providing the insect cell;
interacting a cell-penetrating peptide (CPP) comprising SEQ ID NO: 1 with an RNA to form an RNA-CPP complex
placing the insect cell and the RNA complex in contact with each other
allowing uptake of the RNA complex into the insect cell.
With respect to the limitation (a), Siaussat et al. teach “Identification of steroid hormone signaling pathway in insect cell Differentiation” (Title). Siaussat et al. teach application of double-stranded RNA-mediated interference (dsRNAi) to a provided insect cell line from Plodia interpunctella Lepidoptera (Abstract).
With respect to the limitations (c) and (d), Siaussat et al. teach administration of a carrier compound with the double-stranded RNA (dsRNA) to form a complex via non-covalent interaction. Siaussat et al. teach the dsRNA-carrier complex added directly to cells to allow uptake of the RNA complex into the insect cells (p367, col 1, last para/DsRNAi).
Siaussat et al. did not teach the use of SEQ ID NO: 1 as a carrier to deliver dsRNA.
Tomich et al. teach the use of linear peptides for creating colloidal particles and micelles for delivery of active agents (Abstract). Tomich et al. teach a preferred carrier is an amphipathic peptide comprising FLIVIKKKKK (100% identity to the instant SEQ ID NO: 1) or VLIVIKKKKK (p4, line 21-23; p17, Example 8) to deliver active agents comprising nucleic acids, other therapeutic agents, or radioactive labels (p4, 31-33). Tomich et al. teach highly cationic surface of the peptide particles resulting from oligo-lysine for efficient cellular uptake of nanoparticles (p10, last para to p11. para 1; p12, last para; p17, para 1). Tomich et al. teach delivering active agents to insects by contacting an insect (reading on insect cells) with colloidal particles carrying the active agent. Because Tomich et al. teach advantages of the peptide carrier-nucleic acid complex comprising (i) easily disperse in aqueous solutions and fostering uptake by animal and plant tissues thereby facilitating the delivery of active ingredients to the interior of cells and (ii) the particles also shield the active agent from the external environment, which could prematurely inactivate the active agent. As drug delivery vehicles, the novel colloidal particles can also be used to alter the biological half-life of an active agent (p3, Description), one of ordinary skill in the art would have found it obvious to beneficially use Tomich’s amphipathic peptide comprising FLIVIKKKKK (100% identity to the instant SEQ ID NO: 1) as a carrier to deliver Siaussat’s nucleic acid of dsRNA to facilitate the delivery of dsRNA to the interior of cultured insect cells, reading on the limitation (b) in claim 10. Tomich et al. teach the linear amphipathic peptide carrier is functionally similar/equivalent to branched amphipathic peptide capsules (p11, para 1).
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Siaussat et al. with Tomich et al. because (a) Siaussat et al. teach application of double-stranded RNA-mediated interference (dsRNAi) to a provided insect cell line from Plodia interpunctella Lepidoptera (Abstract) and (b) Tomich et al. teach the beneficial use of an amphipathic peptide comprising FLIVIKKKKK, with 100% identity to the instant SEQ ID NO: 1, (p4, line 21-23) to deliver an active agent of nucleic acids (p4, 31-33) to facilitate the delivery of nucleic acid into cells and shield the active agent from inactivation by the external environment (p3, Description). The combination would have reasonable expectation of success because both references teach administration of nucleic acids into insect cells.
With respect to claim 12, Siaussat et al. teach the treated insect cell line from Plodia interpunctella Lepidoptera (Abstract).
With respect to claim 19, Siaussat et al. teach the dsRNA-carrier complex added directly to cells in cell culture (p367, col 1, last para/DsRNAi). Furthermore, Tomich et al. suggest an active agent (e.g., dsRNA)-amphipathic peptide complex feeding on insects (Example 6, p13-p14), reading on insect cells in vivo
2. Claims 10, 12-13, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Siaussat et al. in view of Tomich et al. as applied to claims 10, 12, 19 and further in view of Ghosh et al. (J. Vis. Exp. 2018; (135), e57390) and De Schrijver et al. (WO 2020/187798 A1).
Claim 13 is drawn to the insect cell as a Hemipteran insect cell.
Siaussat et al. in view of Tomich et al. teach a method of deliver dsRNA into insect cells in vitro and oral delivery of dsRNA in vivo as applied to claims 10, 12, and 19.
PNG
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362
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Greyscale
Siaussat et al. in view of Tomich et al. do not specify the insect cell as a Hemipteran insect cell.
Ghosh et al. teach “Double-stranded RNA Oral Delivery Methods to Induce RNA Interference in Phloem and Plant-sap-feeding Hemipteran Insects” (Title) shown in figure as follows (p5, figure 1). Because Ghosh et al. teach Double-stranded RNA can be introduced into insect cells via oral delivery (feeding) consistent with Tomich et al., one of ordinary skill in the art would have found it obvious to feed dsRNA)-amphipathic peptide complex to a Hemipteran insect cell to inhibit the insect growth and/or kill the insect, reading on claim 13. De Schrijver et al. is further cited to show double stranded RNA molecules targeted to insect genes [Abstract, 0005-0006] in various insect species comprising Coleoptera, Lepidoptera, Diptera, Hymenoptera, Hemiptera, and Trichoptera [0105] as claimed.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Siaussat et al. in view of Tomich et al. with (ii) Ghosh et al. because (a) Siaussat et al. in view of Tomich et al. teach oral delivery of dsRNA-amphipathic peptide complex by feeding on insects (Example 6, p13-p14) and (b) Ghosh et al. teach “Double-stranded RNA Oral Delivery Methods to Induce RNA Interference in Phloem and Plant-sap-feeding Hemipteran Insects” (Title and p5, figure 1). The combination would have reasonable expectation of success because all references teach delivery of nucleic acid (e.g., dsRNA) into insect cells. De Schrijver et al. is further cited to show double stranded RNA molecules targeted to various insect species as claimed.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
20-February-2026
/LI N KOMATSU/Primary Examiner, Art Unit 1658