Prosecution Insights
Last updated: April 18, 2026
Application No. 17/796,086

SINGLE-STRANDED POLYNUCLEOTIDE

Non-Final OA §103§112
Filed
Jul 28, 2022
Examiner
PERSONS, JENNA L
Art Unit
1637
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
National University Corporation Tokai National Higher Education And Research System
OA Round
1 (Non-Final)
52%
Grant Probability
Moderate
1-2
OA Rounds
2y 12m
To Grant
99%
With Interview

Examiner Intelligence

Grants 52% of resolved cases
52%
Career Allow Rate
25 granted / 48 resolved
-7.9% vs TC avg
Strong +73% interview lift
Without
With
+73.4%
Interview Lift
resolved cases with interview
Typical timeline
2y 12m
Avg Prosecution
47 currently pending
Career history
95
Total Applications
across all art units

Statute-Specific Performance

§101
8.0%
-32.0% vs TC avg
§103
27.9%
-12.1% vs TC avg
§102
14.9%
-25.1% vs TC avg
§112
30.0%
-10.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 48 resolved cases

Office Action

§103 §112
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. Application Status A pplicant’s response filed February 9, 2026 is acknowledged. Claims 1-15 are pending. Restriction/Election Applicant’s election of Group I (claims 1-10 ) without traverse in the re sponse filed February 9, 2026 is acknowledged. Accordingly, claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 1-10 are under consideration hereinafter. Priority A pplicant’s priority claims to Application Nos. JP2020-015404 and PCT/JP2021/003332 are acknowledged. Claims 1-10 find support in Application No. JP2020-015404 . The effective filing date of the claims under examination is January 31, 2020. Claim Objections Claim 4 is objected to because of the following informalities: Claim 4 recites “wherein the base length of A 1 and A 2 is 3 or more ... .” Based on the specification’s guidance regarding the palindromic sequence A 1 -B-A 2 ([0043]-[0045]), this limitation is reasonably interpreted as requir ing that the base length of each of A 1 and A 2 is 3 or more. Accordingly, it would be preferable to amend the claim to recite “wherein the base length of A 1 and A 2 is 3 or more , the base length of A 2 is 3 or more … . ” Appropriate correction is required. Claim Rejections - 35 USC § 112(d) 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 5 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 5 recites that “the palindromic structure consists of the acyclic polynucleotide structural unit.” The term “acyclic polynucleotide structural unit” is interpreted as a nucleotide analog comprising an acyclic structure, and no sugar structure ([0032]). The term “palindromic structure” is interpreted as a single-stranded polynucleotide consisting of a base sequence, i.e., any two or more linked nucleotides, that can form a self-duplex ([0041]). Accordingly, in requiring that the palindromic structure “consist[] of” the acyclic polynucleotide structural unit (i.e., a nucleotide analog ) , claim 5 no longer requires all of the features of the palindromic structure required of claim 1 (i.e., a base sequence) , and therefore, no longer includes all of the limitations of the claim upon which it depends. 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. Notice to Joint Inventors 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 Rejections - 35 USC § 103 – Kamiya in view of Murayama and Gamper 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. Claims 1- 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kamiya ( Kamiya et al., 2017, ChemBioChem Communications , 18, pg. 1917-1922 and Supporting Information ; of record ) , in view of Murayama ( Murayama et al., 2013, Chem. Eur. J, 19, pg. 14151-14158 ) and Gamper ( Gamper et al., 2004, Biochemistry, 43, pg. 10223-10236 ). Claim 1 is interpreted as a single-stranded polynucleotide (i.e., any two or more linked nucleotides), comprising a palindromic structure (i.e., any two or more linked nucleotide s which can form a self-duplex structure , [0041]), wherein the palindromic structure comprises an acyclic polynucleotide structural unit (i.e., a nucleotide comprising an acyclic structure, and no sugar structure, [0032]) , and wherein an adenine or adenine analog in the palindromic structure is replaced by diaminopurine , and a thymine or thymine analog at a position complementary to the adenine is replaced by a thiouracil derivative. The palindromic structure may have the base sequence represented by formula (2): A 1 -B-A 2 , wherein A 1 and A 2 are each 3 or more nucleotides in length , A 1 and A 2 are complementary to each other (b ut need not be 100% complementary, provided they hybridize ) , and B is 0 to (base length of A 1 + A 2 /4) nucleotides in length ([0043]-[0045]). Regarding claim s 1 and 4 , Kamiya teaches a single-stranded polynucleotide ( “amiR21-S-D7” ) comprising a palindromic structure (underlined in Fig. A below), comprising an acyclic polynucleotide structural unit ( “SNA ” ) ( Scheme 1; Table 1 , pg. 1918 ) . Kamiya teaches the palindromic structure compris es adenine (italicized in amiR21-SNA, Fig. A below) , which is replaced by diaminopurine ( “D,” bolded in Kamiya , Table 1 and in amiR21-S-D7 in Fig. A below ). A s shown in Fig. B below, the palindromic structure is a single-stranded polynucleotide consis ting of a base sequence represented by formula (2), in which A 1 and A 2 are each 3 or more nucleotides in length , A 1 and A 2 are complementary to each other, and B is one nucleotide in length . FIGURE A. Adapted from Kamiya Table 1 . ( S)-CAAC A TC A GTCTG A T AAGCTA-(R ) amiR21-SNA (S)-C DDC D TC D GTCTG D T DDGCTA -(R ) amiR21-S-D7 FIGURE B . _ A 1 _ _ B __ A 2 _ ( S)-C DDC D TC D G T CTG D T DDGCTA -(R ) amiR21-S-D7 Kamiya does not teach that a thymine at a position complementary to the adenine in the palindromic structure is replaced by a thiouracil derivative. However, Murayama teaches that while polynucleotides comprising SNA , i.e., the acyclic polynucleotide structural unit of Kamiya , can form stable duplexes with both DNA and RNA, these polynucleotides form more stable homoduplexes (i.e., SNA/SNA), even across short sequences (Table s 1 -2 ; pg. 14157, left col. ; Fig. 4 ). Gamper also teaches that substitution with a single base pair stabilizing analogue, e.g., diaminopurine , would be expected to enhance intramolecular pairing (pg. 10234, left col.). Gamper teaches that secondary structures formed from self-hybridization of a probe pose a significant barrier to use of the probe in hybridization-based assays (Abstract; pg. 10224). Gamper proposes a strategy to overcome the “problem of secondary structure,” which utilizes pseudocomplementary bases, diaminopurine and 2-thiouracil, that can form stable base pairs with thymine and adenine, respectively, but not with each other (pg. 10224, right col.; pg. 10225; Fig. 1). Gamper demonstrates that diaminopurine and 2-thiouracil can be incorporated into single-stranded polynucleotides, and that the resulting polynucleotides are less inclined to form duplexed structures , and therefore, more accessible to hybridize to a probe ( pg. 10228-102 30 ; Fig. 5 -7 ). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have replaced the thymine complementary to the diaminopurine -replaced adenines in the palindromic structure of Kamiya’s single-stranded polynucleotide in view of Murayama and Gamper . It would have amounted to applying a known design strategy to reduce homoduplex formation of a single-stranded polynucleotide to a known polynucleotide, by known means to yield predictable results . The skilled artisan would have recognized, based on Murayama, that SNA-modified polynucleotides form more stable duplexes with complementary SNA-modified polynucleotides, than to complementary RNA (e.g., the miR-21 target RNA) . The skilled artisan also would have recognized that the addition of diaminopurine to Kamiya’s polynucleotide further increases the propensity f or homoduplex formation based on Gamper . The skilled artisan, therefore, would have been motivated to replace the thymine complementary to the diaminopurine -replaced adenine in the palindromic structure of Kamiya’s polynucleotide with thiouracil as taught by Gamper , so that the polynucleotide would be more inclined to hybridize to its target RNA, rather than to itself. The skilled artisan would have had a reasonable expectation of success in preparing a thiouracil substituted version of Kamiya’s polynucleotide because as evidenced by the prior art, preparing polynucleotides with a combination of natural bases and analog bases was well within the purview of the skilled artisan. The skilled artisan would have had a reasonable expectation that the resulting thiouracil substituted version of Kamiya’s polynucleotide would be functional because the parent version is functional, and Gamper demonstrates that polynucleotides comprising both diaminopurine and thiouracil are capable of hybridizing to complementary polynucleotides. Regarding claims 2-3, as shown in Fig. C below, the acyclic polynucleotide structural unit of Kamiya’s single-stranded polynucleotide is represented by formula (I), wherein R 1 and R 2 are each hydrogen atoms, and Base is a nucleobase ( Scheme 1, pg. 1918 ). FIGURE C . Adapted from Kamiya Scheme 1 . Regarding claim 5, in view of the § 112(d) issues described above, the claim will be interpreted as requiring a palindromic structure comprising an acyclic polynucleotide structural unit. As described above, Kamiya’s single-stranded polynucleotide comprises a palindromic structure comprising an acyclic polynucleotide structural unit (i.e., SNA). Regarding claim 6, a pplying the thiouracil derivative replacement design taught by Gamper t o Kamiya’s single-stranded polynucleotide results in the polynucleotide in Fig. D below , in which thiouracil derivatives are indicated with “ U .” T he number of diaminopurines and the number of thiouracil derivatives are each two or more in the single-stranded polynucleotide rendered obvious above. FIGURE D . _ A 1 __ B __ A 2 _ ( S)-C DDC D U C D G T C U G D U DDGCTA -(R ) amiR21-S-D7 Regarding claim 7, the single-stranded polynucleotide has a base length within the instantly claimed range (i.e., 21 nucleotides). Regarding claim 8, Kamiya teaches the single-stranded polynucleotide is complementary to a cellular endogenous polynucleotide , i.e., miR-21 ( “miR-21 is an oncogenic miRNA overexpressed in many types of cancer cells. We prepared anti-miR21 oligonucleotide s … (Table 1),” pg. 1918, left col.; “The SNA-AMO with seven D residues (amiR21-S-D7) hybridized to miR-21 had a T m value that was approximately 9 ° C higher than that of the unmodified SNA/miR-21 duplex,” pg. 1919, right col.; Table 1 ). Regarding claim 9, Kamiya teaches the single-stranded polynucleotide is an anti-miRNA ( "We prepared anti-miR21 oligonucleotides… (Table 1) ,” pg. 1918, left col.; “The SNA-AMO with seven D residues (amiR21-S-D7) hybridized to miR-21 had a T m value that was approximately 9 ° C higher than that of the unmodified SNA/miR-21 duplex,” pg. 1919, right col.; Table 1; Fig s . 3-4 ). Regarding claim 10, Kamiya teaches a double-stranded polynucleotide comprising the single-stranded polynucleotide according to claim 1 ( “The SNA-AMO with seven D residues (amiR21-S-D7) hybridized to miR-21 had a T m value that was approximately 9 ° C higher than that of the unmodified SNA/miR-21 duplex,” pg. 1919, right col.; Table 1 ). Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JENNA L PERSONS whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-1334 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F: 9-5pm . 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, FILLIN "SPE Name?" \* MERGEFORMAT JENNIFER A DUNSTON can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (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. /JENNA L PERSONS/ Examiner, Art Unit 1637 /Soren Harward/ Primary Examiner, TC 1600
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Prosecution Timeline

Jul 28, 2022
Application Filed
Mar 30, 2026
Non-Final Rejection — §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
52%
Grant Probability
99%
With Interview (+73.4%)
2y 12m
Median Time to Grant
Low
PTA Risk
Based on 48 resolved cases by this examiner. Grant probability derived from career allow rate.

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