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 January 21, 2026 are acknowledged. Claims 3-7, 10, 24, 26, 27, 30, 32, 34, 36, and 38 have been canceled. Claim 1 was amended. Claims 1, 2, 8, 9, 11-23, 25, 28, 29, 31, 33, 35, 37, and 39-76 are pending.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 21, 2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-10, 13-16, 18-21, and 23-27) in the reply filed on January 17, 2025 is acknowledged.
Applicant’s election without traverse of the following species in the reply filed on January 17, 2025 is acknowledged:
Third paragraph of claims 1 and 11
PNG
media_image1.png
140
635
media_image1.png
Greyscale
miR-122 (claim 3)
Applicant’s response filed on January 17, 2025 was not fully responsive to the species election requirement. It is acknowledged that Applicant elected SEQ ID NO: 105; however, the restriction indicated that the variant of the miRNA from claims 20 and 26 must be a variant of the miRNA elected from claim 3. During a telephone conversation with Mr. Gleb Savich on March 3, 2025, Mr. Savich confirmed species election of miR-122 (claim 3) and further elected SEQ ID NO: 356 (claim 20) for examination. Affirmation of this election must be made by Applicant in replying to this Office action.
It is noted that Applicant’s remarks filed on January 21, 2026 did not affirm the species election that was made on March 3, 2025.
Based on Applicant’s election of miR-122 and SEQ ID NO: 356, SEQ ID NO: 6, miR-122-G7U, miR-122-G7,9U, and SEQ ID NO: 794 read on the elected species.
Claims 11, 12, 17, 22, 28, 29, 31, 33, 35, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 January 17, 2025.
Claims 13-16, 18-21, 39-43, 49-68, and 70-76 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 January 17, 2025.
Claims 1, 2, 8, 9, 23, 25, 44-48, and 69 are examined on the merits herein.
Priority
This application claims priority to PCT/KR2019/006603 filed on May 31, 2019 which claims priority to KR10-2019-0064333, KR10-2019-0064335, KR10-2019-0064386, and KR10-2019-0064334 filed on May 31, 2019 and KR10-2018-0063055 and KR10-2018-0063054 filed on May 31, 2018.
While certified copies of the foreign priority documents were received, translation of the priority documents were not provided. Therefore, priority is given with the effective filing date of May 31, 2019, which is the PCT filing date.
Withdrawn Objections
In view of Applicant’s amendments and response, the objections to the specification are withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the improper Markush grouping and 35 U.S.C 112(a) new matter rejections are withdrawn.
Drawings
The drawings were received on July 14, 2025.
The drawings are objected to because Figure 1 is blurry and difficult to read. 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.
Response to Arguments
Applicant's arguments filed January 21, 2026 have been fully considered but they are not persuasive.
Contrary to Applicant’s assertions, substitute drawings were submitted with Applicant’s remarks. Therefore, the Examiner is maintaining the objection to the drawings.
Specification
The substitute specification filed on January 21, 2026 has been entered.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 8, 9, 23, 25, 44-48, and 69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 23 are drawn to the provision of a genus of RNA interference-inducing nucleic acids defined solely by function to suppress a non-canonical target gene of microRNA (miRNA). The specification filed on January 21, 2026 discloses that the invention is directed to providing an RNA interference-inducing nucleic acid having an effect of efficiently improving biological functions exhibited by suppressing a non-canonical target gene by conventional miRNA or selectively exhibiting one of the biological functions by suppressing a non-canonical target gene by conventional miRNA [page 5, second paragraph].
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification discloses an RNA interference-inducing nucleic acid which suppresses a non-canonical target gene of miRNA by modifying a partial sequence of specific miRNA in one or more single strands of the double strands of the nucleic acid inducing RNA interference wherein the RNA interference-inducing nucleic acid has a modified base sequence in which at least one guanine base is substituted with uracil or adenine preferably in a sequence in positions 2 to 7 based on the 5’ end of a base sequence between 1 to 9 bases from the 5’ end of miRNA such that a G:A or G:U wobble pair at the corresponding site becomes a canonical base pair of U:A or A:U [pages 5-6]. Preferably, an RNA interference-inducing nucleic acid having a base sequence of 5’-UGG AGU UGU GAC AAU GGU GUU-3’ (miR-122-BS) as an RNA interference-inducing nucleic acid suppressing a non-canonical target gene of miR-122 (SEQ ID NO: 6) [page 7]. Preferably, the RNA interference-inducing nucleic acid is any one or more of the base sequences between the 1st to 9th bases from the 5’ end:
PNG
media_image2.png
170
732
media_image2.png
Greyscale
PNG
media_image3.png
720
750
media_image3.png
Greyscale
[pages 8-9]. Preferably, the RNA interference-inducing nucleic acid has one or more of the following base sequences:
PNG
media_image4.png
716
664
media_image4.png
Greyscale
[page 12].
The specification further discloses an RNA interference-inducing nucleic acid suppressing a non-canonical target gene of miRNA by modifying a partial sequence of specific miRNA in one or more single strands of the double strands of the nucleic acid inducing RNA interference wherein the RNA interference-inducing nucleic acid has a modified base sequence in which at least one guanine is substituted with uracil in a base sequence between the second to ninth bases from the 5’ end of specific miRNA and the G:A wobble at the corresponding site becomes the canonical base pair of U:A. Preferably, the RNA interference-inducing nucleic acid includes a sequence of 6 to 8 consecutive bases starting from the second base from the 5’ end of specific miRNA in which at least one guanine base is substituted with a uracil base [page 25]. Preferably, the RNA interference-inducing nucleic acid selectively suppresses only a non-canonical target gene of miRNA binding to a G:A wobble pair and does not suppress a canonical target gene of miRNA [page 26]. Preferably, the RNA interference-inducing nucleic acid has a sequence of 6 to 8 consecutive bases containing 2 to 7 or 2 to 9 bases from the 5’ end represented by any one or more of SEQ ID NOS: 529-863 [page 29].
Working example 10 discloses the discovery of non-canonical target site allowing wobble base pairing at seed position of miRNA through Ago HITS CLIP assay. Specifically, recognition of the non-canonical target of miRNA allows G:A wobble pairing to the seed sequence and it is considered that many miRNAs may bind to the mRNA of a target gene thus inhibiting expression of the gene.
Working example 16 confirmed that miR-122 inhibits expression of the gene having the non-canonical G:A wobble seed site and showed that the efficiency is lower compared to the canonical seed site. In addition, there was an approximately 2-fold difference in inhibitory efficiency when inhibition of gene expression was initiated in a non-canonical G:A wobble seed target compared to a canonical seed target site. Further, it was confirmed that miR-122 is weaker than a canonical seed site and can inhibit the expression of the non-canonical G:A wobble seed target caused by G2 from the 5’ end, and miR-122 naturally present in liver cancer cells inhibits the expression of the non-canonical 3G:A wobble seed target gene and the non-canonical 2,3G:A wobble seed target gene based on the 5’ end.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of a small group of RNA interference-inducing nucleic acids. The results are not necessarily predictive of other RNA interference-inducing nucleic acids falling within the broadly claimed genus not limited to any particular structure. Thus, it is impossible for one to extrapolate from the limited examples described herein those RNA interference-inducing nucleic acids that would necessarily meet the structural/functional characteristics of the rejected claims.
Hill et al. (PLoS ONE 2014) discloses that the mRNA target specificities of miRNAs in animals are primarily encoded within a 7 nt ‘‘seed region’’ mapping to positions 2–8 at the molecule’s 5’ end and substitution of even a single nucleotide within the seed region changes the spectrum of mRNA targets by >50% [abstract].
Although post-filing, Stavast et al. (Cells 2019) discloses that some of the identified non-canonical sites in mammalian cells do not mediate repression of their bound targets. Further, the vast majority of functional miRNA-binding sites are canonical [page 2, last paragraph].
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of RNA interference-inducing nucleic acids that could suppress a non-canonical target gene of microRNA (miRNA).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1, 2, 8, 9, 23, 25, 44-48, and 69.
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, 8, 9, 23, 25, 44-48, and 69 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Claim 1 is drawn to an RNA interference-inducing nucleic acid which suppresses a non-canonical target gene of microRNA (miRNA) wherein the RNA interference-inducing nucleic acid has a modified base sequence produced by substituting at least one guanine with uracil or adenine in a corresponding specific miRNA sequence wherein the substituting is between the first to ninth base from the 5’ end of the miRNA and wherein the substituting replaces a G:A or G:U wobble pair with a U:A or A:U pair.
Claim 8 is drawn to a composition for inhibiting the expression of a non-canonical
target gene of miRNA comprising the RNA interference-inducing nucleic acid of claim 1.
Claim 9 is drawn to a composition for regulating cell cycling, differentiation, dedifferentiation, morphology, migration, division, proliferation or apoptosis comprising the RNA interference-inducing nucleic acid of claim 1.
Claim 23 is drawn to an RNA interference-inducing nucleic acid suppressing a non-canonical target gene of microRNA (miRNA) wherein the RNA interference-inducing nucleic acid has a modified base sequence produced by substituting at least one guanine with uracil in a corresponding specific miRNA sequence wherein the substituting is between the first to ninth bases from the 5’ end of the miRNA wherein the substituting replaces a G:A wobble pair with a U:A pair and wherein the RNA interference-inducing nucleic acid has the sequence of 6-8 consecutive bases starting from the 2nd base from the 5’ end represented by any one of SEQ ID NOS: 529-863.
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 – Claim 1
Step 1 – Is the claim to a Process, Machine, Manufacture or Composition of Matter? YES.
Claim 1 is directed to an RNA interference-inducing nucleic acid which suppresses a non-canonical target gene of microRNA (miRNA) wherein the RNA interference-inducing nucleic acid has a modified base sequence produced by substituting at least one guanine with uracil or adenine in a corresponding specific miRNA sequence wherein the substituting is between the first to ninth base from the 5’ end of the miRNA and wherein the substituting replaces a G:A or G:U wobble pair with a U:A or A:U pair which is a composition of matter.
Claim 8 is drawn to a composition for inhibiting the expression of a non-canonical
target gene of miRNA comprising the RNA interference-inducing nucleic acid of claim 1 which is a composition of matter.
Claim 9 is drawn to a composition for regulating cell cycling, differentiation, dedifferentiation, morphology, migration, division, proliferation or apoptosis comprising the RNA interference-inducing nucleic acid of claim 1 which is a composition of matter.
Claim 23 is drawn to an RNA interference-inducing nucleic acid suppressing a non-canonical target gene of microRNA (miRNA) wherein the RNA interference-inducing nucleic acid has a modified base sequence produced by substituting at least one guanine with uracil in a corresponding specific miRNA sequence wherein the substituting is between the first to ninth bases from the 5’ end of the miRNA wherein the substituting replaces a G:A wobble pair with a U:A pair and wherein the RNA interference-inducing nucleic acid has the sequence of 6-8 consecutive bases starting from the 2nd base from the 5’ end represented by any one of SEQ ID NOS: 529-863 which is a composition of matter.
Therefore, these claims are 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 recites an RNA interference-inducing nucleic acid which suppresses a non-canonical target gene of microRNA (miRNA) wherein the RNA interference-inducing nucleic acid has a modified base sequence produced by substituting at least one guanine with uracil or adenine in a corresponding specific miRNA sequence wherein the substituting is between the first to ninth base from the 5’ end of the miRNA and wherein the substituting replaces a G:A or G:U wobble pair with a U:A or A:U pair. Claims 8 and 9 recite a composition for inhibiting the expression of a non-canonical target gene of miRNA (claim 8) or a composition for regulating cell cycling, differentiation, dedifferentiation, morphology, migration, division, proliferation or apoptosis (claim 9). Claim 23 recites an RNA interference-inducing nucleic acid suppressing a non-canonical target gene of microRNA (miRNA) wherein the RNA interference-inducing nucleic acid has a modified base sequence produced by substituting at least one guanine with uracil in a corresponding specific miRNA sequence wherein the substituting is between the first to ninth bases from the 5’ end of the miRNA wherein the substituting replaces a G:A wobble pair with a U:A pair and wherein the RNA interference-inducing nucleic acid has the sequence of 6-8 consecutive bases starting from the 2nd base from the 5’ end represented by any one of SEQ ID NOS: 529-863.
The claims encompass the naturally occurring gga-mir-122-2 molecule. As evidenced by miRBase, the gga-mir-122-2 sequence (designated as Db) has a modified base sequence produced by substituting G at position 5 from the 5’ end of the mmu-mir-122 molecule (designated as Qy) with A to result in replacement of a G:U wobble pair with an A:U pair The structure of gga-mir-122-2 is also shown below the alignment. Thus as evidenced by miRBase, an RNA interference-inducing nucleic acid having a modified base sequence produced by substituting at least one guanine with a uracil or adenine in a corresponding specific miRNA sequence wherein the substituting is between the 1st to 9th base from the 5’ end of the miRNA and wherein the substituting replaces a G:A or G:U wobble pair with a U:A or A:U pair is naturally occurring.
PNG
media_image5.png
170
584
media_image5.png
Greyscale
Structure of gga-mir-122-2:
PNG
media_image6.png
130
364
media_image6.png
Greyscale
Structure of mmu-mir-122:
PNG
media_image7.png
118
282
media_image7.png
Greyscale
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, 8, 9, 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, 8, 9, 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, 8, 9, 23, 25, 44-48, and 69 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.
Response to Arguments
Applicant's arguments filed January 21, 2026 have been fully considered but they are not persuasive.
Applicant asserts that all of the sequences recited in the claims are modified forms of naturally occurring miRNA sequences and do not exist in nature. Applicant further asserts the following:
PNG
media_image8.png
638
802
media_image8.png
Greyscale
PNG
media_image9.png
714
706
media_image9.png
Greyscale
These arguments are not found persuasive. As an initial matter, it should be noted that Applicant uses miR-124 as an example in its arguments however the elected species was miR-122. In addition, Applicant points to Figure 10D when referring to the G:A and G:U base pairings; however, it appears that Applicant may have intended to point to Figure 10C instead (reproduced below) because Figure 10D is a bar graph.
PNG
media_image10.png
320
680
media_image10.png
Greyscale
Nonetheless, contrary to Applicant’s assertions, the claims as currently written still read on naturally occurring miRNAs and do not provide an application as outlined in the 35 U.S.C. 101 rejection above. Thus, the claims are drawn to patent-ineligible subject matter.
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.
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, Jennifer Dunston can be reached on (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637