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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on January 5, 2026.
Currently, claims 1-5 and 8 are pending and under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Response to Arguments
Applicant’s arguments filed on January 5, 2026 have been considered but are moot because they do not pertain to the new objections/rejections necessitated by amendments as set forth hereinbelow.
New Objections/Rejections Necessitated by Amendment
Drawings
The drawings filed on January 5, 2026 is objected to because of the following informalities:
1. The replacement drawings filed on January 5, 2026 identify the same nucleotide sequence by two different sequence identifiers. See for instance the nucleotide sequence having the identifier “SEQ ID NO: 45” in FIG. 2b and that having the identifier “SEQ ID NO: 68” in FIG. 3a. Note that a nucleotide sequence must be identified by a single sequence identifier, not multiple sequence identifiers. Applicant is required to review the entire replacement drawings and make appropriate corrections.
2. The nucleotide sequence information in the replacement drawings filed on January 5, 2026 is inconsistent with that in the sequence listing. For instance, compare SEQ ID NO:72 in FIG. 3a filed on January 5, 2026 with SEQ ID NO:72 in the sequence listing, each reproduced below.
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As shown above, the two nucleotide sequences having the identical sequence identifier are different. Applicant is required to review the entire replacement drawings and make appropriate corrections.
3. The replacement drawings filed on January 5, 2026 are also objected to for failing to provide correct legend. See FIG. 2c, for instance, providing the identical information for “No coating” and “DNMT1” as reproduced below.
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Applicant is required to review the entire replacement drawings and make appropriate corrections.
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.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 recites duplicate SEQ ID NOs. See for instance “SEQ ID NO: 48” recited twice. Appropriate correction is required.
Claim Rejections – Improper Markush Grouping
Claims 1-5 and 8 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
In the remarks filed on January 5, 2026, applicant argues that all SEQ ID NO species recited in the instant claims “share a common use” as an aptamer. See page 8. In response, it is noted that an improper Markush grouping includes species that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The very fact that applicant is unable to provide evidence that all of the alternatively recited 71 individual SEQ ID NOs share a common nucleotide sequence and a common use flowing from the commonly shared nucleotide sequence.
If the species of a Markush claim does not share one of (either) a common, single structural similarity or a common use, then the claim is an improper Markush claim because the species fail to satisfy both the common structural similarity and the common use. That is, the mere fact that all 71 SEQ ID NOs (including the delicately recited SEQ ID NOs) have a common use as an aptamer is not sufficient to show that all alternatively recited species constitute a proper Markush claim.
Note that the instant rejection is judicially approved as set forth in “Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. 112 and for Treatment of Related Issues in Patent Applications” in Federal Register, Volume 76, Number 27, published on February 9, 2011, which expressly states the following:
“A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use…When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.” (emphasis added). See page 7166, middle column.
The 71 different SEQ ID NOs recited in claim 1 and dependent claims thereof do not all share a common nucleotide sequence. Again, as explained in the last Office action, the only significant homology between applicant’s elected SEQ ID NO:68 (same as SEQ ID NO:45 having the name “Ce-49”) and SEQ ID NO:71 is a 6-mer sequence (5’-CUGAGG). In fact, the 6-mer homology is not even at the same nucleotide positions between the species. That is, the two sequences have to be shifted a significant number of nucleotides in order to obtain the 6-mer homology. See the nucleotide sequence alignment between SEQ ID NO:68 and SEQ ID NO:71 as shown below, wherein the vertical lines show the matched nucleotides.
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Since applicant failed to show that all of the alternatively recited 71 nucleotide sequences in the claims share both a significant nucleotide sequence similarity and a common aptamer use, this rejection is hereby reiterated.
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.
Claims 3-4 are 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 3 recites that the aptamer of claim 1 comprises a stem structure comprising at least two nucleotide pairs and/or a loop structure comprising at least four nucleotides. It is noted that the RNA sequences newly recited in claim 1 inherently form the secondary structure(s) recited in claim 3. Hence, claim 3 fails to further limit the subject matter of claim 1.
Claim 4 recites that the aptamer of claim 1 comprising one of 71 SEQ ID NOs “is an RNA-aptamer.” It is noted that the recited SEQ ID NOs including applicant’s elected SEQ ID NO:68 are RNA sequences. Hence, the “aptamer” of claim 1 comprising one of 71 SEQ ID NOs is inherently an RNA aptamer. As such, claim 4 fails to further limit the subject matter of claim 1.
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 § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5 and 8 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 1 and all of dependent claims thereof are currently amended to recite “DNMT1-interactingRNA:ecCEBPA”. In the remarks filed on January 5, 2026, applicant points out page 6 of the specification that the term is art-recognized. Contrary to applicant’s argument, page 6 merely spells out the abbreviated term “DiR” but fails to define “DNMT1-interactingRNA:ecCEBPA”. Since the recited limitation is not defined in the specification or in the claims, the clear metes and bounds cannot be ascertained.
Claim 5 recites that the aptamer of claim 1 comprising one of 71 SEQ ID NOs “comprises between 10 and 61 nucleotides”. It is noted that none of the 71 specifically recited SEQ ID NOs is as short as 10 nucleotides. Hence, the aptamer that comprises one of the recited SEQ ID NOs cannot comprise only “10” nucleotides or any nucleotide length shorter than the recited SEQ ID NOs. As such, the length range recited in claim 5 conflicts with the structural requirement that the claimed aptamer should comprise one of the recited SEQ ID NOs, none of which are close to being 10 nucleotides in length, wherein the conflicting structural limitations recited in claim 5 renders the structure of the claimed aptamer indefinite.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5 and 8 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.
The instant claims require that any of the recited SEQ ID NO should be capable of inhibiting DNMT1, wherein claim 2 specifically requires that any one of the recited SEQ ID NOs “is capable of reducing DNMT1 function by at least about 30%,” “is capable of increasing CEBPA (CCAAT/enhancer-binding protein alpha) levels,” and “is capable of reducing the viability of a cancerous cell.”
The instant specification fails to support the requisite structure-function correlation for all of the recited SEQ ID NOs having the recited functions. Interestingly, the instant application itself expressly demonstrates a high level of unpredictability pertaining to the actual function of the recited SEQ ID NOs as evidenced by the results illustrated in FIG. 2c showing the drastically different (about 3-fold) DNMT1 binding affinity between two aptamer sequences, see “Ce-10” and “Ce-49”, sharing about 64% sequence homology as shown below, wherein the boxed sequences are matched between the two sequences.
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Now, it is noted that the recited SEQ ID NOs in the instant claims appear to share some nucleotides in the 5’ end and/or 3’ end as in between Ce-10 and Ce-49, which showed about a 3-fold difference in DNMT1 binding affinity, wherein a short sequence match/homology between two SEQ ID NOs is not predictive of similar target binding function. It is noted that the specification at best describes that “Among the tested sequences”, only two species, one of which is applicant’s elected species of SEQ ID NO:68, have the desired level of binding to endogenous DNMT1, thereby resulting in reduced DNMT1 function by at least about 40% as well as reduced cancer cell viability. See pages 37-39. Given the unpredictable nature of aptamer sequences in providing actual function as noted above, applicant’s elected species, SEQ ID NO:68, is not deemed a representative aptamer sequence for all of the recited SEQ ID NOs in the rejected claims for providing the recited functions including reducing cancer viability and reducing DNMT1 function by at least about 30%. Accordingly, the instant specification fails to adequately describe the requisite structure-function correlation for all of the recited SEQ ID NOs in the rejected claims.
Double Patenting
The text of the judicially created doctrine not included in this action can be found in a prior Office action.
Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,941,399 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claim reciting at least 10 nucleotides of recited SEQ ID NOs is anticipated by the ‘399 patent claims. For instance, SEQ ID NO:9 recited in claim 5 comprises at least 10 consecutive nucleotides of the oligonucleotide sequence claimed in the ‘399 patent claims, thereby anticipating claim 5 reciting that the aptamer is at least 10 nucleotides in length.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANA H SHIN/Primary Examiner, Art Unit 1635