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 .
DETAILED ACTION
Status of Application/Amendment/Claims
Applicant's response filed 03/19/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 11/19/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 03/19/2026, claims 16, 18, 21, 23-30 and new claims 32-34 are pending in the application.
The 103 and 112(a) rejections are withdrawn in response to claim amendments and Applicant’s arguments.
The Double Patenting rejections over co-pending Application No. 17,595,993 and Patent 11,312,954 are withdrawn in response to claim amendments and Applicant’s arguments.
Claims 16, 18, 21, 23, 25-30 and new claims 32-34 are free of the prior art as explained below.
Claim 24 is rejected.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejection not reiterated in this Office Action is hereby withdrawn.
Maintained Rejections
Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §§ 1.821-1.825 for the reason(s) set forth on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821 - 1.825) before the application can be examined under 35 U.S.C. §§ 131 and 132.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – the CRF is defective for the following reasons and as cited on the CRFD mailed 04/01/2026:
This validation report concerns the sequence listing filed 03-31-2026 17:00:22 and indicates the errors found by the USPTO during validation of the sequence listing. Any resolution of the errors identified in this validation report should not be construed as meaning that the sequence listing will comply with all of the requirements of 37 CFR
§§ 1.821- 1.825, WIPO Standard ST.25, 37 CFR §§ 1.831-1.835 and 1.839, or WIPO Standard ST.26. For any sequence listing related questions or concerns, the Applicant is invited to contact the USPTO Sequence Help Desk at 571-272-2510 or SequenceHelpDesk@USPTO.GOV
Reviewer's Comments
1. Missing Title:
The title "Sequence Listing" is missing.
The sequence rules state the sequence file must start with the title "Sequence
Listing".
Sec. 1.823: Requirements for nucleotide and/or amino acid sequences as part of the
application papers. (a) The ``Sequence Listing'' required by Sec. 1.821 (c), setting
forth the nucleotide and/or amino acid sequences and associated information in
accordance with paragraph (b) of this section, must begin on a new page and must be
titled ``Sequence Listing''
Please add the title "Sequence Listing" at the beginning of the sequence listing file,
above the <110> field.
2. For SEQ ID# 1-19 has improper feature section for organism name as "Artificial sequence" in numeric
identifier "<213>". Please see a detailed explanation below to make all necessary corrections.
numeric identifier <213> can only be one of three choices, "Scientific name, i.e.
Genus/species, Unknown or Artificial Sequence." Numeric identifier <213> cannot be the name of a gene, name of a protein, or the name of a fragment of DNA, RNA, or protein.
Suggest using "Artificial sequence" for numeric identifier <213> and "Primer" for
numeric identifier <223> in the mandatory feature. For all sequences using "Unknown" or
"Artificial sequence", for numeric identifier <213>, a mandatory feature is required to
explain the source of the genetic material. The feature consists of numeric identifier
<220>, which remains blank and, numeric identifier <223>, which states the source of the genetic material.
Please make all necessary changes.
New 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 24 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 pre-AIA the applicant regards as the invention.
Claim 24 lack antecedent basis because it recites “the chromosomal rnr gene” and depends from claim 23 and 16 that do not recite this limitation.
Closest prior art
The prior art does not teach the claimed invention and the claimed invention would not have been obvious to one of ordinary skill in the art. The prior art of Keates et al. (Pharmacogenomics, 2007, 8:867-871 of record 892 mailed 11/19/2025), teach a Transkingdom RNAi vector wherein the technology uses nonpathogenic E. coli comprising a prokaryotic promoter engineered to produce an shRNA from plasmid (TRIP) containing Inv which permits entry into cells and HlyA genes which permit escape of the shRNA. Keates et al. teach efficient in vitro expression of shRNA against a beta-catenin gene and teach efficient oral administration to mice that lead to significant reduction of beta-catenin protein levels (Figure 3).
The prior art of Okuda et al. (Enhanced gene delivery and/or efficacy by functional peptide and protein. Curr Top Med Chem. 2009;9(12):1098-1108 cited on IDS filed 05/01/2024) and Huang ("Unique 2′-O-methylation by Hen1 in eukaryotic RNA interference and bacterial RNA repair." Biochemistry 51.20 (2012): 4087-4095 of record 892 mailed 11/19/2025) teach a dsRNA binding protein and a HEN1 protein, respectively. Okuda et al. teach (dsRBP) has been shown to regulate signaling events and gene expression in cells and demonstrates in a vector expressing a dsRBP and shRNA, shRNA had a higher stability in cells and Haung teach Hen1 methylates the 2′-OH group at the 3′-terminal nucleotide of a small RNA, resulting in inhibition of uridylation and thus stabilizing the RNA (right) (Figure 3 and page 4090). These references do not teach a reason to express these proteins from a nonpathogenic E. coli in a nucleic acid delivery vehicle as instantly claimed.
Given that Keates et al. demonstrates efficient in vitro and in vivo inhibition of expression using a nucleic acid targeted to a gene and using a Transkingdom RNAi vector comprising a nonpathogenic E. coli, it would not have been obvious to try expressing a dsRNA binding protein or a HEN1 protein from the bacterium because Keates does not identify a problem to be solved such that one would want to express either of these proteins from the bacterium. Keates et al. efficiently demonstrates inhibition of expression using a therapeutic nucleic acid and therefore one of skill in the art would not have any motivation or reason to add proteins to reduce intracellular degradation as this was not demonstrated as a problem in the prior art.
Conclusion
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).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at 571-272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
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