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 .
The claims filed 11/21/2025 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-14 and 16-20, in the reply filed on 11/21/2025 is acknowledged.
Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/21/2025.
Priority
The present application is a 371 national stage entry of PCT/GB2021/052502 (filed 9/24/2021), which claim foreign priority to EPO 20425038.5 (filed 9/24/2020).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on submitted IDS, they have not been considered.
Drawings
The drawings filed 3/20/2023 are objected to because Figs. 4 and 6 disclose nucleotide sequences that are not identified with SEQ ID NOs.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. Figs. 4 and 6 disclose nucleotide sequence not identified with SEQ ID NOs.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The embedded hyperlinks that reference websites are on pages 7, 9, 13, 15, 24 and 37.
The use of terms that are trade names or marks used in commerce, such as NuPAGE™ and Qiagen®, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. While NuPAGE™ has been properly identified, others such as Qiagen® have not been proper identified.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 14 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). The scope of claim 1 and claim 14 are identical as the only structure required by claim 14 is that of claim 1.
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 14 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 14 depends from claim 1 and it requires all the structural elements of claim 1 by referencing claim 1 in the body of the claim. Claim 14 does not require any other structural elements beyond that of claim 1 and thus fails to further limit the scope of claim 1. In other words the scope of claim 1 and claim 14 are identical.
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
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 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(s) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gustincich (WO 2019/058304 A1; cited on the 2/19/2024 IDS).
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Regarding claims 1, 2, 3, 4, 5, 6, 12 and 14, Gustincich teaches a Target-specific SINEUP “functional nucleic acid” as depicted in Figure 2A, reproduced below with Examiner’s annotations mapping claim elements:
The “target determinant sequence” has a sequence that hybridizes with the target nucleic acid as depicted above (p. 40, lines 3-10).
The “regulatory sequence” comprises a SINE B2 family transposable element (p. 40, lines 1-3).
While Figure 2A does not describe the SINEUP as having “one or more chemical modifications”, Gustincich teaches an analogous molecule for increasing translation of target mRNA that includes modified RNA, including: modified bases pseudouridine and 5'-methylcytidine; sugar modifications 2'-O-methyl (2'-O-Me) and 2' -O-methoxyethyl (2' -MOE); and other modifications GalNAc linkage (hepatocytes).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have incorporated the modifications described by Gustincich into the SINEUP “functional nucleic acid”. One would have been motivated to make the modifications because it allows the SINEUP of Gustincich to be delivered as naked RNA and to increase the RNA stability (p. 38, lines 4-6). The modification has a reasonable expectation as the SINEUP and trans-acting “functional nucleic acid” molecule of Gustincich are each RNA molecules designed to increase the translation of a target RNA molecule.
Regarding claims 7, 8 and 9, Gustincich teaches an IRES “regulatory sequence” (p. 20, line 18 to p. 21, line 6) or the entire “functional nucleic acid molecule” (p. 22, lines 2-13), may include the above noted modifications.
It would have been prima facie obvious at the time of invention to have tried placing the various modifications in different regions of the “SINEUP”, molecule including the “target determinant sequence” and/or the “regulatory sequence” in order to evaluate which modifications and where they are placed leads to RNA stability and increased translation.
Regarding claims 10 and 11, Gustincich teaches the “target determinant sequence” hybridizes with a sequence spanning the AUG sequence of the target mRNA and includes the 5’ UTR region upstream of the AUG sequence and the CDS downstream of the AUG sequence as depicted in Figure 2A above.
Gustinich further teaches the binding domain or “target determinant sequence” is 18 nucleotides in length (p. 64, lines 3-6).
Regarding claim 20, Gustincich teaches “functional nucleic acids” are encapsulated in lipid-based nanoparticles as a “carrier” (p. 38, lines 1-10).
Claim(s) 13, 17 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gustincich (WO 2019/058304 A1) in view of Zhang (US 2018/0291400 A1).
Regarding claims 13, 17 and 18, Gustincich renders obvious the elements of claim 1 as required by claims 13, 17 and 18 as described above.
Gustincich does not teach the additional elements specific to claims 13, 17 and 18.
However, Zhang teaches design features of synthetic, modified RNAs, such as those of Gustincich.
Regarding claim 13, Zhang teaches including 5’ caps or poly(A) tails in synthetic, modified RNAs (para. 188).
Regarding claims 17 and 18, Zhang teaches including two modified nucleotides in synthetic, modified RNAs, including N6-methyladenosine and 2’-O-methyladenosine (para. 188).
It would have been prima facie obvious to the ordinary artisan at the time of invention to have modified the composition of Gustincich by incorporating the structures of Zhang. One would have been motivated to do so because it aids in the stability of the synthetic, modified RNAs and protects them from nuclease degradation (para. 264, 273). The modification has a reasonable expectation of success as it incorporates known RNA structures and nucleotide structures having known functions and properties into RNA molecules using known techniques.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gustincich (WO 2019/058304 A1) in view of Wesselhoeft (Nature Communications. 2018. 9:2629).
Regarding claim 16, Gustincich renders obvious the elements of claim 1 as required by claim 16 as described above.
Gustincich does not teach the additional elements specific to claim 16.
However, Wesselhoeft teaches design features of synthetic, modified RNAs, such as those of Gustincich.
Regarding claim 16, Wesselhoeft teaches that circular RNA is resistant to exonuclease-mediated degradation because they lack free ends (p. 2 of 10). Wesselhoeft further teaches methods for engineering and generating circular RNA (p. 2 of 10 and p. 8-9 of 10).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have modified the composition of Gustincich by rendering it circular. One would have been motivated to do so because it renders the synthetic RNA resistant to nuclease degradation as taught by Wesselhoeft. The modification has a reasonable expectation of success as it applies the RNA design and generation techniques of Wesselhoeft to the RNA of Gustincich.
Conclusion
Claim 19 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682