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 August 28, 2025.
Currently, claims 44-63 are pending in the instant application.
Newly submitted claims 55, 57, and 60-63 are directed to nonelected species/invention. Note that applicant elected without traverse product claims with species election of C/EBPalpha saRNA in the reply filed on May 14, 2025.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 55, 57, and 60-63 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Accordingly, claims 44-54, 56, and 58-59 are 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Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.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 with respect to the previous rejections of claims 16-17, 24-25, 29, 31, and 39-41, which are now cancelled, have been considered but are moot because the arguments do not pertain to the new rejections necessitated by the claim amendments as set forth hereinbelow.
New Objections/Rejections Necessitated by Amendment
Drawings
The drawings were received on August 28, 2025. These drawings are not accepted because Figures 1C and 2B contain new matter. The original Figures 1C and 2B contained legends for each of the four bases (A, C, G, U), which are not in the replacement drawings. Hence, the deletion of the originally contained subject matter in Figures 1C and 2B introduces new matter. Appropriate correction is required.
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 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 44 and 47 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.
Claims 44 and 47 are drawn to a compound consisting of a sequence as set forth as SEQ ID NO:14 or SEQ ID NO:15.
It is noted that the nucleotide sequence of SEQ ID NO:14 and that of SEQ ID NO:15 are 100% identical. See the two sequences reproduced from the sequence listing as shown below.
PNG
media_image1.png
38
402
media_image1.png
Greyscale
PNG
media_image2.png
40
392
media_image2.png
Greyscale
In view of the identical nucleotide sequence between the two different SEQ ID NOs, it is unclear as to why two identical compounds - one comprising “a nucleic acid consisting of a sequence as set forth as” SEQ ID NO:14 and the other comprising “a nucleic acid consisting of a sequence as set forth as” SEQ ID NO:15 - should be claimed in order to claim an identical “nucleic acid consisting of a sequence”.
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 44-46, 48-49, 51, 53-54, 56, and 58-59 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 are drawn to a nucleic acid consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:11, or SEQ ID NO:12, which constitutes a pharmaceutical composition.
The terms “nucleic acid” and the “compound” comprising the nucleic acid are used to refer to a nucleic acid “capable of binding the transferrin receptor” as evidenced by paragraph 0003 of the instant specification.
The instant specification fails to describe the structure-function correlation for the 87-mer sequence of SEQ ID NO:11 and the 16-mer RNA sequence of SEQ ID NO:12 as there is no sufficient support for such correlation. In fact, SEQ ID NO:11 is only listed in the sequence listing such that the 92-page substitute specification filed on August 28, 2025 is completely silent regarding SEQ ID NO:11. Further, SEQ ID NO:12 is merely mentioned in paragraph 0164 as following: “In some embodiments, the nucleic acid sequence comprises or consists of SEQ ID NO: 12.” Such generic disclosure of SEQ ID NOs:11-12 in the instant application is far from adequately describing the function of SEQ ID NOs:11-12 as being “capable of binding the transferrin receptor” to the extent that SEQ ID NOs:11-12 can constitute a pharmaceutical composition.
Regarding SEQ ID NOs:4-5, the specification expressly discloses that “the two truncates without 5’-GGG, TR14 ST1-1 and TR14 ST1-2, were not internalized into the cells (FIG. 2C). However, interestingly, the TR14 ST1-3 was internalized in both HepG2 cells and PANC-1 (FIG. 2C).” (emphasis added). See paragraph 0331. See also paragraph 0340 disclosing that for “binding affinity” for hTFR1 assays show that “neither TR14 ST-1-1 nor TR14 ST1-2 were measurable.” It is noted that “TR14 ST1-1” is identified as SEQ ID NO:4 and “TR14 ST1-2” is identified as SEQ ID NO:5. Hence, the specification expressly discloses that SEQ ID NOs:4-5 do not have the required aptamer function of binding to the transferrin receptor.
In view of the foregoing, it is concluded that the instant specification fails to adequately describe the purported aptamer function of SEQ ID NOs:4-5 and 11-12 thus fails to reasonably convey that the instant co-inventors had possession of the aptamer nucleic acids consisting of SEQ ID NOs:4-5 and 11-12 recited in claims 44-46, 48-49, 51, 53-54, 56, and 58-59 as of the filing date sought in the instant application.
Claim Rejections - 35 USC § 103
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 44, 46, 48, 50, 56, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Rossi et al. (US 2017/0226515 A1) in view of Saetrom (US 2016/0298113 A1, of record).
Rossi teaches making a pharmaceutical composition comprising the TfR aptamer that is “about 46 nucleotides in length” comprising SEQ ID NO:3 that is linked to a “therapeutic moiety” that is “C/EBPalpha saRNA”, which is “capable of activating the expression of a C/EBPalpha protein.” See paragraphs 0093-0094, 0096, 0106, 0111-0112.
Rossi discloses SEQ ID NO:3 in paragraph 0140 as shown below.
PNG
media_image3.png
52
550
media_image3.png
Greyscale
It is noted that the above RNA sequence is identical to the 43-mer sequence at positions 1-43 of SEQ ID NO:2 claimed in the instant case.
Rossi discloses the original, untruncated TfR aptamer sequence of SEQ ID NO:1 in paragraph 0140 as shown below, wherein underline has been added for the 40-mer sequence at positions 4-43 of Rossi’ SEQ ID NO:3.
PNG
media_image4.png
68
551
media_image4.png
Greyscale
Rossi does not expressly teach that the “46 nucleotides in length” comprising the 43-mer SEQ ID NO:3 has the additional 3-nt sequence 5’-AUG at positions 44-46. Rossi also does not disclose SEQ ID NO:9 for the “C/EBPalpha saRNA”.
Saestrom discloses C/EBPalpha saRNA “XD-03302 CEBPA” comprising SEQ ID NO:280 (5’-GCGGUCAUUGUCACUGGUCUU), wherein the saRNA activates and increases CEBPA mRNA levels in cells. See Table 18-1 and 20.
It is noted that Saestrom’s SEQ ID NO:280 is 100% identical to SEQ ID NO:9 claimed in the instant case.
It would have been obvious to one of ordinary skill in the art before the effective filing date to make a 46-mer RNA sequence consisting of SEQ ID NO:2 claimed in the instant case as a variant of a TfR aptamer comprising Rossi’s SEQ ID NO:3. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because making a 46-mer comprising SEQ ID NO:3 was expressly taught and suggested by Rossi, and because the nucleotide sequence information available to make a 46-mer comprising the 43-mer sequence of Rossi’s SEQ ID NO:3 was expressly disclosed by Rossi as evidenced by Rossi’s SEQ ID NO:1.
It would also have been obvious to one of ordinary skill in the art before the effective filing date to use Saestrom’s SEQ ID NO:280 as the “therapeutic moiety” when making Rossi’s composition comprising “C/EBPalpha saRNA” that is attached to the TfR aptamer. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Saestrom’s saRNA was already demonstrated to activate/increase the CEBPA mRNA expression, which would have been reasonably deemed to increase the expression level of a CEBPA protein, thereby suggesting that Saestrom’s saRNA fully satisfies the description of Rossi’s “C/EBPalpha saRNA” that is “capable of activating the expression of a C/EBPalpha protein” thus is suitable when making Rossi’s composition.
Accordingly, claims 44, 46, 48, 50, 56, and 59 taken as a whole would have been prima facie obvious before the effective filing date.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 44, 46, 48, 50, 56, and 59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,236,341 B2 in view of Rossi et al. (US 2017/0226515 A1) and Saetrom (US 2016/0298113 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed aptamer and the aptamer attached to a C/EBPalpha saRNA would have been obvious over and encompassed by the ‘341 patent claims drawn to an aptamer “comprising” SEQ ID SEQ ID NO:3. It was known in the art to make a 46-mer RNA aptamer comprising SEQ ID NO:3 as evidenced by Rossi, wherein it would have been obvious to any person of ordinary skill in the art that additional 3 bases are required in order to make a 46-mer RNA aptamer sequence comprising the 43-mer sequence of SEQ ID NO:3, wherein the untruncated, full-length aptamer sequence was known (see Rossi’s SEQ ID NO:1), from which the instantly claimed 46-mer sequence of SEQ ID NO:2 could have been more than reasonably obtained. Further, the saRNA sequence claimed in the instant case was known as evidenced by Saetrom. Accordingly, the instantly claimed subject matter would have been obvious over the ‘341 patent claims.
Claims 44, 46, 48, 52, 54, 56, and 59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,427,826 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed aptamer is anticipated by the ‘826 patent claims drawn to and require an aptamer that is “a length of 29 nucleotides or fewer” or “22 nucleotides or fewer” or “16 nucleotides in length” that “is capable of binding to a transferrin receptor (TfR)”, wherein the aptamer is linked to a C/EBPalpha saRNA moiety. It is noted that the aptamer that is “22 nucleotides” is defined to read on SEQ ID NO:1 (5’-UUUAUUCACAUUUUUGAAUUGA), which is expressly claimed in claim 3, and the aptamer that is “16 nucleotides” is defined to read on SEQ ID NO:5 (5’-AUUCACAUUUUUGAAU) in the ‘826 patent specification (see column 2), which is claimed in claim 6. It is noted that the ‘826 patent’s SEQ ID NO:1 is 100% identical to SEQ ID NO:6 claimed in the instant case, and SEQ ID NO:5 is 100% identical to SEQ ID NO:12 claimed in the instant case. It is noted that the broadly claimed C/EBPalpha saRNA moiety claimed in the ‘826 patent claims is defined to read on SEQ ID NO:9 and SEQ ID NO:10 as evidenced by column 28 of the ‘826 patent specification, wherein SEQ ID NOs:9-10 of the ‘826 patent are 100% identical to SEQ ID NOs:9-10 claimed in the instant case.
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.
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.
/DANA H SHIN/Primary Examiner, Art Unit 1635