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
Applicant's preliminary amendment filed on June 8, 2022 is acknowledged. Claims 3-5, 11-15, 18, 20, and 22 were amended. Claims 1-23 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-14 and 23) in the reply filed on August 1, 2025 is acknowledged.
Applicant’s election of the following species: a region composed of an snRNA sequence in the reply filed on August 1, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 14 is drawn to a nucleic acid encoding the guide RNA according to claim 1. Claim 14 was inadvertently included in Group I (drawn to a guide RNA) and should have been included in Group II.
Claims 14-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 August 1, 2025.
Claims 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 1, 2025.
Claims 1-7, 13, and 23 are examined on the merits herein.
Priority
This application claims priority to PCT/JP2020/045707 filed on December 8, 2020 which claims priority to JP2019-222437 filed on December 9, 2019.
While certified copies of the foreign priority documents were received, translation of the priority document was not provided. Therefore, priority is given with the effective filing date of December 8, 2020, which is the PCT filing date.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 8, 2022, June 25, 2022, November 16, 2023, October 2, 2024, December 20, 2024, January 17, 2025, and July 10, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Citation numbers A17 and A22 of the IDS submitted on June 8, 2022 were lined through because these references were listed on the IDS submitted on June 25, 2022 which reflect the correct publication year for A17 and correct volume number for A22. It is noted that both of the references were only submitted on June 8, 2022.
The listing of references in 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, they have not been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract is not limited to a single paragraph. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The use of the term NucleoBond, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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
Claims 1 and 11 are objected to because of the following informalities:
Claim 1 recites the abbreviation ADAR. The abbreviation should be clearly written out at their first occurrence in the claim and should be followed by the abbreviation in parentheses.
Claim 11, line 5 recites “base sequence to from” and should recite “base sequence to form” (emphasis added).
Appropriate correction is required.
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.
Claims 4 and 23 are 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 4 is indefinite at the recitation of “having any one or more functions among functions including” because the metes and bounds of the functions is unclear. The use of the open-ended words “among functions including” renders the claim indefinite because it is unclear what other alternatives are intended to be encompassed by the claim.
Claim 23 recites the limitation "the guide RNA". There is insufficient antecedent basis for this limitation in the claim. It would be remedial to amend the preamble to state, “A guide RNA” in place of “A polynucleotide.” However, it is noted that such an amendment would make claim 23 a duplicate of claim 1.
Claim Rejections - 35 USC § 102
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 1-4, 13, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cox et al. (Science 2017).
Regarding claim 1, the clause “for editing a target RNA by ADAR” is the preamble and is interpreted as intended use of the invention while the body of the claim sets forth all the limitations. See MPEP 2111.02(II).
Regarding claims 1, 2, 13, and 23, Cox et al. teaches a system referred to as RNA Editing for Programmable A to I Replacement (REPAIR) which edits RNA by using catalytically inactive Cas13 (dCas13) to direct adenosine-to-inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to transcripts in mammalian cells [abstract]. Cox et al. shows in Figure 1A (reproduced below) a guide RNA comprising at least one functional region (hairpin) and an antisense region that’s complementary to a portion of the target RNA (spacer).
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Regarding claim 3, Cox et al. analyzed whether the identity of the base opposite the target A in the spacer sequence affected editing efficiency and found that an A-C mismatch had the highest luciferase restoration, in agreement with previous reports of ADAR2 activity, with A-G, A-U, and A-A having drastically reduced REPAIRv1 activity [page 4, right column, first paragraph].
Regarding claim 4, the structure in the prior art is indistinguishable from the structure in this claim, and absent evidence to the contrary the recited limitation “wherein the functional region is a region including a base sequence having any one or more functions among functions including stabilization of the guide RNA, localization of the guide RNA to a nucleus, localization of the guide RNA to cytoplasm, promotion of double strand formation between the target RNA and the antisense region, inhibition of non-specific double strand formation by the antisense region, and stabilization of a complex formed of the target RNA and the antisense region” is a function that is an inherent property of the structure. See MPEP 2112.
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.
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.
Claims 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Cox et al. (Science 2017) as applied to claims 1-4, 13, and 23 above, and further in view of Gerbi et al. (Molecular Biology of the Cell 2002) and Montiel-Gonzalez et al. (Methods 2019).
Regarding claims 5-7, the teachings of Cox et al. are discussed above.
However, Cox et al. does not teach that the functional region is composed of an snRNA sequence.
Gerbi et al. teaches that spliceosomal U6 small nuclear RNA (snRNA) transiently passes through the nucleolus. All individual snRNAs of the [U4/U6.U5] tri-snRNP localize to nucleoli. Further, nucleolar localization of U6 is independent from [U4/U6] snRNP formation since sites of direct interaction of U6 snRNA with U4 snRNA are not nucleolar localization elements [abstract].
Montiel-Gonzalez et al. teaches that Adenosine Deaminases that Act on RNA (ADARs) are a group of enzymes that catalyze the conversion of adenosines (A’s) to inosines (I’s) in a process known as RNA editing [abstract]. Montiel-Gonzalez et al. also teaches that most ADARs are concentrated within the nucleolus although small amounts must be present in the greater nucleoplasm to carry-out editing at endogenous sites [page 18, right column, second full paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the guide RNA of Cox et al. by incorporating a snRNA sequence such as a U6 snRNA sequence because Gerbi et al. taught that U6 snRNA localizes to the nucleus and Montiel-Gonzalez et al. taught that most ADARs are concentrated within the nucleolus. One would have been motivated to do so because it would have amounted to combining prior art elements according to known methods in order to achieve the predictable result of RNA editing by ADARs as taught by Montiel-Gonzalez et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/ Supervisory Patent Examiner, Art Unit 1637