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 . 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.
Election/Restrictions
Applicants elected SEQ ID 1 attached to a modified anti-miRNA-21 without traverse in the reply filed on 6 March, 2026.
Claims Status
Claims 1, 3, and 5-34 are pending.
Claim 1 has been amended.
Claims 3, 7-11, 13-21, 23, 24, and 27-34 have been withdrawn due to an election/restriction requirement.
Maintained/Modified Objections
Specification
The disclosure is objected to because of the following informalities: applicants have listed sequences without their SEQ ID number, note paragraphs 117, 119, 122, 124, etc. The MPEP states that "37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application” (MPEP 2422.03).
Appropriate correction is required.
response to applicant’s arguments
Applicants state that they have amended the specification to correct this.
Applicant's arguments filed 18 June, 2026 have been fully considered but they are not persuasive.
While applicants have corrected most of the issues, they appear to have missed at least one (paragraph 156).
Drawings
The drawings are objected to because they show sequences without the appropriate SEQ ID number, note fig 1, for example. The MPEP states that "It should be noted that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the sequence listing and the sequence identifier ("SEQ ID NO:X") must be used, either in the drawing or the brief description of the drawings” (MPEP 2422.02). 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 applicant’s arguments
Applicants state that they have amended fig 1 to correct this.
Applicant's arguments filed 18 June, 2026 have been fully considered but they are not persuasive.
Applicants have removed the nucleotide sequence and replaced it with the phrase “SEQ ID 2.” However, they have left the peptide sequence (PD-L1 peptide sequence). Note that it is not necessary to remove the polypeptide or polynucleotide sequence, but wherever a sequence is given, it must have the appropriate SEQ ID number.
Withdrawn Rejections
The rejection of claims 1, 4-6, 12, 22, 25, and 26 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to uncertainty as to what sequences will bind PD-L1 is hereby withdrawn due to amendment.
Claims 1, 2, 4-6, 12, 22, 25, and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph due to uncertainty as to what a modified nucleic acid entails is hereby withdrawn due to amendment.
The rejection of claims 1, 2, 4-6, 12, 22, 25, and 26 on the ground of nonstatutory double patenting as being unpatentable over claim 1, 6, and 12 of U.S. Patent No. 11,015,197 in view of Lu et al (CN 112717141) is hereby withdrawn due to the filing of a proper terminal disclaimer.
Maintained/Modified Rejections
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(s) 1, 5, 6, 12, 22, 25, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al (CN 112717141, published April, 2021, priority to Feb, 2021) in view of Drakaki et al (J. Clin. Oncol (2017) 35(33) suppl.). Note that Lu et al is in Chinese. A machine translation is used for this rejection, and all references to locations in the reference refer to the machine translation unless otherwise noted.
Lu et al discuss a doxorubicin conjugated to a peptide to target cancer (abstract). The peptide is highly specific for PD-L1 (8th page, 7th paragraph). A working example used the sequence NYSKPTDRQYHFK with an azido group attached to the N-terminus as the targeting sequence (10th page, 5th paragraph), which was reacted with an acetylene derivative of doxorubicin (drawing at center of 10th page). Note that this comprises applicant’s elected sequence. This is also the material that was used for further testing (8th page, 10th through 13th paragraphs) which shows that it was of interest to the authors of the paper. The material was synergistic compared to doxorubicin or the peptide alone, and was of lower toxicity and had fewer side effects than the chemotherapeutic alone (12th page, 8th paragraph). Utility is for treating a large number of different cancers, such as lung, prostate, and bladder cancers (4th page, claim 9). Material was dissolved in PBS (10th page, 6th paragraph), a pharmaceutically acceptable diluent.
The difference between this reference and the examined claims is that this reference does not discuss an oligonucleotide attached to the peptide.
Drakaki et al discuss an miRNA21 inhibitor in bladder cancer (title), which is one of the cancers that Lu et al state their conjugate can be used for. The inhibitor is an antisense oligo with a LNA phosphorothioate backbone (6th and 7th lines of abstract). In vivo treatment reduced the growth and invasiveness of a bladder cancer model (14th and 15th likes of abstract). This reference describes a modified antisense miRNA 21 agent for treatment of cancer.
Therefore, it would be obvious to substitute the miRNA21 inhibitor of Drakaki et al for the doxorubicin of Lu et al, as a substitution of one known element (the doxy of Lu et al) for another (the miRNA21 inhbitor of Drakaki et al) yielding expected results (treatment of cancer). As both Lu et al and Drakaki et al describe treatment of bladder cancer, and the miRNA inhibiter alone was effective, an artisan in this field would attempt this modification with a reasonable expectation of success.
The combination of references renders obvious a PD-L1 binding peptide of SEQ ID 1 conjugated to a modified miRNA, rendering obvious claim 1.
The oligonucleotide is a modified anti-miRNA 21, rendering obvious claims 5, 6, 12, and 22.
Lu et al discusses formulations in PBS, rendering obvious claim 25.
Claim 26 describes an intended use. There is nothing in the construct rendered obvious by Lu et al and Drakaki et al that makes it unsuitable for such use, rendering the claim obvious (MPEP 2122).
response to applicant’s arguments
Applicants point out differences between the cited references and their claims, and state that no motivation was given to combine.
Applicant's arguments filed 18 June, 2026 have been fully considered but they are not persuasive.
It is agreed that neither reference anticipates applicant’s claims. However, as this is a rejection under 35 USC 103, rather than 35 USC 102, there is no need for a given citation to list every limitation of the claims, so long as the combination of citations render the claims obvious.
Applicants argue that there is no motivation to combine. Teaching-suggestion-motivation is just one rationale that can be used for combining references in an obviousness rejection, but other rationales, such as the one used in this rejection, are also valid (MPEP 2145 (X)(C)).
New Rejection
Claim Rejections - 35 USC § 112(b)
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 1, 5, 6, 12, 22, 25, and 26 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 claims dependent on it, is open, but the peptide sequence is closed (consisting of a sequence of SEQ ID NO: 1). However, if an embodiment is found that has elements beyond SEQ ID 1, it is not clear if they are intended as part of the PD-L1 binding element or not. In other words, there exist embodiments that either read on the claims or not depending only on the intent of the person who designed them.
Conclusion
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone 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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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