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
This application is a 371 of PCT/US2022/034697 filed 06/23/2022.
This application also has PRO of 63214056 filed 06/23/2021.
Accordingly, claims 1-2, 4-14, 16, 19, and 23-31 of this instant application are afforded the effective filing date of 06/23/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/20/2024 and 01/27/2026 have been considered by the examiner and initialed copies of the IDS are included with the mailing of this office action.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 2, 4-14, 16, 19, and 23-27, in the reply filed on 01/27/2026 is acknowledged. Applicant also elected the nucleotide sequence of SEG ID NO:1 as the species of hydrophilic NA head group and Formula I as the species of hydrophobic dialkyl tail comprising a hydrophobic spacer. However, upon further consideration, the Examiner hereby withdraws the election of species requirement and extends the search to all species of hydrophilic NA head group, and hydrophobic dialkyl tail comprising a spacer.
Claims 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group/invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/27/2026.
Status of the Claims
Claims 1, 2, 4-14, 16, 19, and 23-31 are pending in this instant application, of which claims 28-31 are withdrawn at this time being drawn to a nonelected group/invention.
Claims 1, 2, 4-14, 16, 19, and 23-27 are examined herein on the merits for patentability.
Claim Objections
Claims 2, 4, and 13 are objected to because of the following informalities: it is suggested that when an acronym (“NA”) is recited for the first time in an independent claim, the acronym is followed by its full description (chemical name) (i.e., “nucleic acid (NA)”). Appropriate correction is required.
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.
Claim(s) 1, 4-14, 19, 24 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kokkoli et al (US 2017/0218367 A1) in view of Lin et al (US 2020/0085742 A1).
Regarding claims 1, 4 and 13, Kokkoli teaches nanostructures such as nanotube comprising nucleic acid (NA)-amphiphiles, each NA amphiphile comprising a hydrophilic NA headgroup and a hydrophobic dialkyl tail containing a hydrophobic spacer, wherein the nanotube is loaded with a therapeutic agent (Abstract; [0004]-[0188]; claims 1-43).
However, Kokkoli does not expressly teach the anti-cancer agent of claims 1 and 4 and the microRNA (miRNA), miRNA mimic, anti-miRNA, or a small interfering RNA (siRNA) as part of the hydrophilic NA headgroup of claim 13.
Regarding the anti-cancer agent of claim 1 and 4 and the microRNA (miRNA), miRNA mimic, anti-miRNA, or a small interfering RNA (siRNA) as part of the hydrophilic NA headgroup of claim 13, Lin teaches a self-assemble nanostructure comprising nucleic acid conjugated to a hydrophobic dialkyl tail (a lipid), wherein the nucleic acid is a DNA, RNA, small interfering RNA (siRNA), microRNA, or antisense oligonucleotide (Abstract; [0059]-[0073], [0082]-[0096], [0142], [0162]-[0209], [0310]-[0319]; claims 44-54). Lin teaches the nanostructure contains a therapeutic agent including anti-cancer drugs such as doxorubicin, and paclitaxel ([0063], [0084], [0102], [0170], [0173], [0178], and [0207]). Lin teaches the nanostructure is a rod-shaped (nanotube) ([0142]).
It would have been obvious to one of ordinary skill in the art in incorporate anti-cancer drug such as doxorubicin or paclitaxel as the therapeutic agent in the nanotube of Kokkoli, and the produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Kokkoli and Lin are commonly drawn to self-assemble nanostructures that are used for delivering therapeutic agents and/or target certain biological molecules and/or detect certain proteins, and Lin provided the direct guidance for incorporating anti-cancer drugs such as doxorubicin, and paclitaxel as the therapeutic agent for delivery from nanostructure (nanotube), as the nanostructure can enhance the delivery of the anti-cancer drugs to tumor sites, thereby enhancing anticancer efficacy (Lin: [0003], [0170], [0204], [0217]). Thus, an ordinary artisan seeking to enhance anticancer efficacy would have looked to incorporate anti-cancer drugs such as doxorubicin and paclitaxel as the therapeutic agent in the nanotube of Kokkoli, and achieve Applicant’s claimed invention with reasonable expectation of success.
It would also have been obvious to one of ordinary skill in the art to incorporate RNA such as small interfering RNA (siRNA) or microRNA, as the nucleic acid that is part of the hydrophilic NA headgroup of Kokkoli, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Kokkoli teaches that RNA is a suitable nucleic acid and Lin provided the guidance to do so by teaching that aside from DNA, RNA such as small interfering RNA (siRNA) or microRNA is a suitable nucleic acid for conjugating with a hydrophobic dialkyl tail (a lipid) to form the self-assemble nanostructure (Lin: Abstract; [0062], [0073], [0082], [0095]-[0096, [0170, [0176] and [0177]). Thus, it would have been merely simple substitution of one known nucleic acid for another to obtain predictable results of nanostructure (nanotube) containing nucleic acid-amphiphiles, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 5, Kokkoli teaches the hydrophilic NA headgroup contains a nucleotide sequence GGGGGTTCTC ([0155]-[0222]).
Regarding claim 6, Kokkoli teaches the hydrophilic NA headgroup contains a single stranded DNA or RNA ([0036], [0041] and claims 34-36).
Regarding claim 7, Lin teaches and provide guidance for using double stranded RNAs as the nucleic acid ([0163]).
Regarding claims 8 and 9, as discussed above, Kokkoli teaches the hydrophilic NA headgroup contains a nucleotide sequence GGGGGTTCTC.
Regarding claim 10, Kokkoli teaches the hydrophobic dialkyl tail comprises
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([0174]-[0191], [0220][-[0222]).
Regarding claim 11, Kokkoli teaches the nucleic acid amphiphiles contains a linker between the hydrophilic NA headgroup and the hydrophobic dialkyl tail (Abstract; [0059]-[0073], [0082]-[0096], [0142], [0162]-[0209], [0310]-[0319]; claims 44-54).
Regarding claim 12, Li teaches and provide guidance for using disulfide linker as the linker between the hydrophilic NA headgroup and the hydrophobic dialkyl tail ([0063] and [0311]-[0312).
Regarding claim 14, Li teaches and provide guidance for using suitable miRNA including miR-21, miR-15, miR-16, miR-146 and miR-29 ([0167 and [0174]).
Regarding claim 19, as discussed above, Kokkoli teaches the nucleic acid amphiphiles contains a linker between the hydrophilic NA headgroup and the hydrophobic dialkyl tail. Li also teaches and provide guidance for linker between the RNA (small interfering RNA (siRNA) or microRNA) and the hydrophobic dialkyl tail (lipid ([0155], [0263] and [0311]).
Regarding claim 24, Kokkoli teaches the hydrophilic NA headgroup containing a nucleotide sequence GGGGGTTCTC is part of the exterior shell of the nanotube ([0155]-[0222]).
Regarding claim 26, Li teaches and provide guidance for incorporating RNA (small interfering RNA (siRNA) or microRNA) as part of a coating layer around the nanostructure ([0072], [0076], [0078], [0176], [0179], [0188]-[0189] and [0192]).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kokkoli et al (US 2017/0218367 A1) in view of Vinayak et al (Anti-Cancer Agents in Medicinal Chemistry, 2019, 19: 1-19).
Regarding claim 2, Kokkoli teaches nanostructures such as nanotube comprising nucleic acid (NA)-amphiphiles, each NA amphiphile comprising a hydrophilic NA headgroup and a hydrophobic dialkyl tail containing a hydrophobic spacer, wherein the nanotube is loaded with a therapeutic agent (Abstract; [0004]-[0188]; claims 1-43).
However, Kokkoli does not expressly teach the senotherapeutic agent of claim 2.
Regarding the senotherapeutic agent of claim 2, Vinayak teaches nucleic acid conjugated nanostructures containing quercetin (a senotherapeutic agent), wherein said nanostructures provide improved stability and bioavailability of quercetin, as well as, provide controlled drug release, long retention in tumor, and enhanced anticancer potential of quercetin (Abstract; pages 1-11).
It would have been obvious to one of ordinary skill in the art in incorporate a senotherapeutic agent such as quercetin as the therapeutic agent in the nanotube of Kokkoli, and the produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Kokkoli and Vinayak are commonly drawn to self-assemble nanostructures that are used for delivering therapeutic agents, and Vinayak provided the direct guidance for incorporating quercetin as the therapeutic agent for delivery from nanostructure (nanotube), as the nanostructure provide improved stability and bioavailability of quercetin, as well as, provide controlled drug release, long retention in tumor, and enhanced anticancer potential of quercetin. Thus, an ordinary artisan seeking to improved stability and bioavailability of quercetin, as well as, provide controlled drug release, long retention in tumor, and enhanced anticancer potential of quercetin would have looked to incorporating quercetin as the therapeutic agent in the nanotube of Kokkoli, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 16 and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kokkoli et al (US 2017/0218367 A1) in view of Lin et al (US 2020/0085742 A1), as applied to claims 1 and 13 above, and further in view of Zhang et al (Advanced Materials, 2018, 30 (1703658): 1-44).
The nanotubes of claims 1 and 13 are discussed above, said discussion being incorporated herein its entirety.
However, Kokkoli and Lin do not teach the anti-miRNA of claims 16 and 27.
Regarding the anti-miRNA of claims 16 and 27, Zhang teaches self-assemble DNA nanostructures (nanotubes) containing anti-miRNA such as anti-MIR 21, wherein the delivery of anti-MIR 21 from the nanostructure efficiently inhibit and further eradicate tumor cells, as the use of anti-miRNA further enhance the selectivity and efficacy of chemotherapy (Abstract; pages 1-15 and 27-35).
It would have been obvious to one of ordinary skill in the art to incorporate anti-miRNA such as anti-MIR 21 as part of the hydrophilic NA headgroup of Kokkoli, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Kokkoli and Zhang are commonly drawn to self-assemble DNA nanostructures (nanotubes) and Zhang provided the guidance to do so by teaching that aside from DNA and RNA, anti-miRNA such as anti-MIR 21 is a suitable nucleic acid for conjugating with a hydrophobic dialkyl tail (a lipid) to form the self-assemble nanostructure that efficiently inhibit and further eradicate tumor cells, as well as, enhance the selectivity and efficacy of chemotherapy. Thus, an ordinary artisan seeking to enhance anticancer efficacy, would have looked to incorporating anti-miRNA such as anti-MIR 21 as part of the hydrophilic NA headgroup of Kokkoli, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 23 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kokkoli et al (US 2017/0218367 A1) in view of Lin et al (US 2020/0085742 A1), as applied to claim 1 above, and further in view of Raemdonck et al (Advanced Drug Delivery Reviews, 2013, 65: 1123-1147).
The nanotube of claim 1 is discussed above, said discussion being incorporated herein in its entirety.
However, Kokkoli and Lin do not teach the polymer or polysaccharide, respectively, of claims 23 and 25.
Regarding claims 23 and 25, Raemdonck teaches polysaccharide assisted nucleic acid delivery from nanostructures, wherein the polysaccharide is coated on the nanostructure so as to enhance intracellular delivery of nucleic acid as well as, lengthen their circulation time in the bloodstream by reduced MPS recognition (Abstract; pages 1124-1142). Raemdonck teaches chitosan, alginate, dextran, and hyaluronic acid as the suitable polysaccharide (Abstract; pages 1124-1142).
It would have been obvious to one of ordinary skill in the art to add a coating layer containing a polysaccharide such as chitosan, alginate, dextran, or hyaluronic acid on the nanotube of Kokkoli and Lin, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Raemdonck provided the guidance to do so by teaching the benefits of adding a coating layer containing a polysaccharide such as chitosan, alginate, dextran, or hyaluronic acid on the nanostructure to assist delivery of nucleic acid by enhancing intracellular delivery of nucleic acid as well as, lengthen their circulation time in the bloodstream by reduced MPS recognition. Thus, an ordinary artisan seeking to enhance intracellular delivery of nanotube of Kokkoli and Lin would have looked to adding a coating layer containing a polysaccharide such as chitosan, alginate, dextran, or hyaluronic acid on the nanotube, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Pertinent prior art: Fotin-Mleczek et al (US 2019/0040378 A1) teaches nucleic acid complexing with lipid nanostructures, wherein suitable nucleic acid include nucleotide sequence containing CTCTTGGGGG (SEQ ID 52193).
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613
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