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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan. The copy has been made available from the WIPO Digital Access Service. The certified copy provides support for the priority date to be the filing date of the foreign application; i.e., Oct 25th, 2019. However, should a certified English language translation of the foreign priority application be required, the priority date must be perfected by providing a certified English language translation of the foreign priority application. See MPEP 213.04(g)(3).
Nevertheless, current rejections do not depend upon the priority date.
Acknowledgement is also made of Applicant’s National Stage entry of PCT Application
PCT/JP2020/040071 filed on Oct 26th, 2020.
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 38 - 45 drawn to a delivery enhancer comprising a folic acid-cationic oligopeptide complex wherein the cationic oligopeptide wherein the cationic oligopeptide comprises a cationic oligopeptide moiety consisting of 8 – 40 amino acids, comprising at least two contiguous amino acid residues of formula I) in the reply filed on 29th August, 2025, was previously acknowledged. Claims 46 - 57 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/29/2025. The withdrawal is made final.
Applicants have since cancelled elected claims 39-41.
Amendments
This action is in response to papers filed 30th Jan 2026, in which claims 38, 43, and 45 were amended, no claims were canceled, and no new claims were added. All of the amendments have been thoroughly reviewed and entered.
Applicant has amended:
specification, to overcome objections; the previous objections are withdrawn.
claim 38 to overcome the 112(b) and (a) rejections; the 112(b) and (a) rejection of all claims is withdrawn.
Applicant’s arguments, see Pgs. 11 - 12, filed 30th Jan 2026, with respect to:
rejections of claims under 35 USC § 103 have been fully considered but are not persuasive for the reasons discussed in this office action. The 35 USC § 103 rejection is maintained.
Arguments applicable to amended claims are addressed below. Arguments that are no longer relevant are not addressed.
Rejections not reiterated here are withdrawn.
Status of Claims
Claims 38 and 42 - 58 are under consideration.
Claim Rejections - 35 USC § 103
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.
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.
Claims 38 and 42 - 58 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda (Bioorganic & Medicinal Chemistry, 2013, Vol.21, pp.1717-1723, IDS) in view of Xiao (Xiao Chemistry A Asian Journal, Vol 13, No. 24, pp.3845-3849, 2018).
Regarding the phrase, “a delivery enhancer of siRNA or shRNA”, which is a preamble of claim 38, see MPEP 2111.02 (II) for significance of preamble in examining. See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation").
Regarding claim 38, Maeda taught RNA/RNA duplex- binding molecules that are useful as drug delivery systems (DDSs) for siRNAs (introduction). Such binding molecules are cationic oligopeptides comprising a variety of natural and unnatural amino acids. See Tables 1 and 2 of Maeda showing the various physicochemical properties of a variety of cationic oligopeptides. The cationic oligopeptides increase the thermal stability of nucleic acid duplexes (abstract). A cationic oligopeptide 8mer consisting of Dab can bind to the major groove of an A-type RNA/RNA duplex 12mer (Fig. 2). In the table one of skill can see that an octamer of Dab (Dab8) shows superior properties than octamers of natural amino acids.
Regarding claims 43-44, Maeda taught the incorporation of glycine (Gly) linkers helps control the distance between the cationic functional groups and peptides with different flexibility (pg. 1718, 1st para left column) and insertion of Gly did not affect the thermal stability of the peptide–RNA complexes (abstract).
Maeda lacks a teaching on folic acid.
However, before the effective filing date of instant invention, Xiao had taught cationic oligopeptides are widely used to deliver nucleic acids. See recitations from pg. 385, 2nd para:
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Xiao taught folate receptors are highly expressed on the membrane of cancer cells (HeLa cells, pg. 3845, last para). Xiao taught Folic acid containing nanocomplexes comprising inhibitory RNA molecules (miRNA, abstract, title) enhance cellular delivery of the inhibitory nucleic acids via ligand–receptor interaction (abstract). Since Xiao teaches the structure of a folate-cationic oligopeptide complex, it would fulfil the purpose of performing as a siRNA or shRNA delivery enhancer because Xiao have demonstrated its use for a structurally similar nucleic acid; i.e., miR-34 delivery.
Regarding claim 42, Xiao teaches folic acid is attached to the C-terminus of the cationic oligopeptide via a linker (through click chemistry, summary para on pg. 3848).
It would have been prima facie obvious to an artisan of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the cationic oligopeptide of the folic acid-cationic oligopeptide conjugate as taught by Xiao with the cationic oligopeptide taught by Maeda into a single structure to make a nucleic acid enhancer of siRNA or shRNA, as claimed. One would be motivated to do so to gain the advantage of targeting cancer cells, conferred by folic acid. One would have had reasonable expectation of success because all of the claimed elements were disclosed by Maeda and Xiao and one skilled in the art could have made this substitution by known methods, also taught by Xiao, with no change in their respective functions, and the combination would have yielded predictable results i.e., an enhancer of nucleic acid delivery of the instant invention. See MPEP 2143 I.(B) and 2142 II.
Regarding claim 45, the combination of prior art elements taught by Xiao and Maeda, when combined would result in all the limitations of instant claim 45.
Regarding claim 58, the combination of prior art elements taught by Xiao and Maeda, when combined would result in an electrically neutral compound, which is salt.
Thus, Maeda in view of Xiao makes obvious instant claims 38, 42-45, and 58.
Response to Remarks
Applicant submits, Pgs. 11 – 12 of Remarks, that the amendments to the Claims remedy the rejections raised in the prior Action. Specifically, “Xiao only teaches "a folate-cationic oligopeptide complex called FA-R9 (scheme 2) comprising 9 consecutive arginine residues and folic acid ... " and claim 38 is amended to: "homomultimer of L-2,4-diaminobutyric acid (Dab) consisting of 8 to 12 amino acids", Dab is not arginine, and Xiao includes no teaching or suggestion of the viability of substituting Dab for arginine”.
Examiner agrees that Xiao does not teach Dab. However, Maeda does; i.e., the limitations of the amended claims were taught individually by the references cited. Further, the courts have stated “[A] prior art reference must be considered in its entirety, i.e., as a whole” W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983) (see MPEP 2141.02VI). MPEP 2123 II clearly states that “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). In the instant case, the cationic oligopeptide, FA-R9 (scheme 2), taught by Xiao, is not relied upon in instant rejection rather only the folic acid conjugated to a cationic oligopeptide is. The cationic oligopeptide, Dab is taught by Maeda.
Therefore, Applicant’s amendments can be rendered obvious by Maeda in view of Xiao.
Conclusion
No claims are 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/ Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635