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 amendments and remarks filed on April 29, 2026 are acknowledged. Claim 5 has been canceled. Claims 1, 4, 6, 8, 10, 11, and 23 were amended. Claims 1-4 and 6-23 are pending.
This action is NON-FINAL due to new grounds of rejection not necessitated by amendment.
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)).
Claims 14-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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Claims 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 1-4, 6, 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.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections
In view of Applicant’s amendments and response, the objection to the specification in reference to the use of a trade name or a mark is withdrawn.
In view of Applicant’s amendments and response, the claim objections are withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 112(b), 35 U.S.C 102, and 35 U.S.C 103 rejections are withdrawn.
Specification
It is noted that the amendment to the abstract filed on April 29, 2026 does not comply with the requirements of 37 CFR 1.121(b) because the full text of the abstract is not shown with markings relative to the immediate prior version. Therefore, the amendment to the abstract has not been entered.
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).
Response to Arguments
Applicant's arguments filed April 29, 2026 have been fully considered but they are not persuasive.
It is noted that the amendment to the abstract filed on April 29, 2026 does not comply with the requirements of 37 CFR 1.121(b) because the full text of the abstract is not shown with markings relative to the immediate prior version. Therefore, the amendment to the abstract has not been entered.
Claim Objections
Claim 4 is objected to because of the following informality:
Claim 4 is missing “(ii)” before the recitation of “localization of the guide RNA to a nucleus” thus the subsequent numbering should be re-numbered accordingly as “(iii)”, “(iv)”, “(v)”, and “(vi)”.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 4, 6, 7, and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception, which is a product of nature without significantly more.
Claim 1 (and dependent claims 2, 4, 6, and 7) is drawn to “A guide RNA…comprising at least one functional region and an antisense region that is complementary to a portion of the target RNA and can form a double strand with the target RNA, wherein the at least one functional region is linked to the antisense region, wherein the guide RNA does not substantially contain an ADAR-recruiting base sequence, and wherein the functional region is a region composed of an snRNA sequence, a region composed of an rRNA sequence, a region composed of a base sequence to form a guanine quadruplex structure, or a region composed of a base sequence to form a stem-loop structure, or any combination thereof.”
Claim 23 is drawn to “A polynucleotide…comprising at least one functional region and an antisense region that is complementary to a portion of the target RNA and can form a double strand with the target RNA, wherein the at least one functional region is linked to the antisense region, wherein the polynucleotide does not substantially contain an ADAR-recruiting base sequence, and wherein the functional region is a region composed of an snRNA sequence, a region composed of an rRNA sequence, a region composed of a base sequence to form a guanine quadruplex structure, or a region composed of a base sequence to form a stem-loop structure, or any combination thereof.”
As outlined below, this judicial exception is not integrated into a practical application, and does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes – Claims 1 and 23
Step 1 – Is the claim to a Process, Machine, Manufacture or Composition of Matter? YES.
Claim 1 (and dependent claims 2, 4, 6, and 7) is directed to a guide RNA which is a composition of matter. The claim is directed to a statutory category.
Claim 23 is directed to a polynucleotide which is a composition of matter. The claim is directed to a statutory category.
Step 2A, Prong One – Does the claim recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES.
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. MPEP 2106.04(c) outlines the markedly different characteristics analysis.
Claim 1 (and dependent claims 2, 4, 6, and 7) is drawn to a guide RNA…comprising at least one functional region and an antisense region that is complementary to a portion of the target RNA and can form a double strand with the target RNA, wherein the at least one functional region is linked to the antisense region, wherein the guide RNA does not substantially contain an ADAR-recruiting base sequence, and wherein the functional region is a region composed of an snRNA sequence, a region composed of an rRNA sequence, a region composed of a base sequence to form a guanine quadruplex structure, or a region composed of a base sequence to form a stem-loop structure, or any combination thereof.
Claim 23 is drawn to a polynucleotide…comprising at least one functional region and an antisense region that is complementary to a portion of the target RNA and can form a double strand with the target RNA, wherein the at least one functional region is linked to the antisense region, wherein the polynucleotide does not substantially contain an ADAR-recruiting base sequence, and wherein the functional region is a region composed of an snRNA sequence, a region composed of an rRNA sequence, a region composed of a base sequence to form a guanine quadruplex structure, or a region composed of a base sequence to form a stem-loop structure, or any combination thereof.”
Kole et al. (US 2003/0036519) indicates that Figure 2 is the wild-type U7 snRNA which contains a stem-loop structure, the U7-specific Sm sequence, and a sequence antisense to the 3' end of histone pre-mRNA [0011]. Therefore, the claimed guide RNA and polynucleotide are not markedly different from its naturally occurring counterpart. Thus, claims 1 (and dependent claims 2, 4, 6, and 7) and 23 recite a product of nature judicial exception.
Step 2A, Prong Two – Does the Claim recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
In the instant case, claims 1 (and dependent claims 2, 4, 6, and 7) and 23 do not recite any elements in addition to the judicial exception (i.e., natural product) that would integrate the natural product into a practical application.
Step 2B – Does the Claim recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claim as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05).
As stated above, claims 1 (and dependent claims 2, 4, 6, and 7) and 23 do not recite any elements in addition to the judicial exception (i.e., natural product). There are no additional elements to amount to significantly more than the judicial exception.
Thus, claims 1, 2, 4, 6, 7, and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon or a law of nature without significantly more.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 4, 6, 7, and 23 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Kole et al. (US 2003/0036519) as evidenced by Lesman et al. (Human Gene Therapy 2021).
Regarding claim 1, the clause “for editing a target RNA by Adenosine Deaminase Acting on RNA (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, 6, 7, and 23, Kole et al. teaches in Figure 2 (reproduced below) a U7 snRNA construct (heavy line) with a stem-loop structure (e.g., a hairpin), a U7-specific Sm sequence (open box) and a sequence antisense to the 3' end of histone pre-mRNA (stippled box) [0011].
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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 selected from (i) stabilization of the guide RNA, localization of the guide RNA to a nucleus, (ii) localization of the guide RNA to cytoplasm, (iii) promotion of double strand formation between the target RNA and the antisense region, (iv) inhibition of non-specific double strand formation by the antisense region, and (v) 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. Although post-filing, as evidenced by Lesman et al., the U7 snRNP involved in histone RNA 3’ end processing has three major components: (1) a histone downstream element (HDE)-binding sequence, (2) a Sm/Sm-like binding site, and (3) a 3’ stem-loop that stabilizes the RNA [page 1318, right column, first full paragraph].
Claims 1, 2, 4, 6, 7, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huang et al. (Microbiological Research 2019) as evidenced by Gerbi et al. (Molecular Biology of the Cell 2002).
Regarding claims 1, 2, 6, 7, and 23, Huang et al. teaches using the 568-bp U6 promoter and the 138-bp U6 terminator from Aspergillus oryzae to control sgRNA transcription [page 47, right column, first paragraph]. Figure 1B (reproduced below) depicts the sgRNA expression cassette.
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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 selected from (i) stabilization of the guide RNA, localization of the guide RNA to a nucleus, (ii) localization of the guide RNA to cytoplasm, (iii) promotion of double strand formation between the target RNA and the antisense region, (iv) inhibition of non-specific double strand formation by the antisense region, and (v) 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. As evidenced by Gerbi et al., all individual snRNAs of the [U4/U6.U5] tri-snRNP localize to nucleoli [abstract].
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Microbiological Research 2019) as evidenced by Gerbi et al. (Molecular Biology of the Cell 2002) as applied to claims 1, 2, 4, 6, 7, and 23 above, and further in view of Turunen et al. (US 2019/0218552).
Regarding claim 3, the teachings of Huang et al. are discussed above.
However, Huang et al. does not teach wherein the antisense region comprises a base to form a mismatched base pair with the target RNA.
Turunen et al. teaches that AONs that are complementary to a target RNA for deaminating a target adenosine present in a target RNA sequence to which the AON is complementary, but—importantly—lack a recruitment portion, are capable of harnessing ADAR enzymes to edit the target adenosine. In a preferred aspect the AON comprises a mismatch at the position of the target adenosine, wherein the opposite nucleotide is a cytidine [0031].
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 Huang et al. wherein the antisense region comprises a base to form a mismatched base pair with the target RNA because Huang et al. taught a sgRNA expression cassette comprising a functional region and an antisense region and Turunen et al. taught that AONs that are complementary to a target RNA comprising a mismatch for deaminating a target adenosine present in a target RNA sequence are capable of harnessing ADAR enzymes to edit the target adenosine. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Microbiological Research 2019) as evidenced by Gerbi et al. (Molecular Biology of the Cell 2002) as applied to claims 1, 2, 4, 6, 7, and 23 above, and further in view of Cox et al. (Science 2017; reference previously cited by the Examiner).
Regarding claim 13, the teachings of Huang et al. are discussed above.
However, Huang et al. does not teach a system for editing a target RNA comprising the guide RNA according to claim 1 and ADAR.
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].
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 system of Cox et al. wherein the system comprises the guide RNA according to claim 1 and ADAR because Cox et al. taught 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) and Huang et al. taught a sgRNA expression cassette comprising a functional region and an antisense region. One of ordinary skill in the art would have made such a modification because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
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
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