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 14, 2026.
Currently, claims 1-21 are pending in the instant application. Claims 13-16 and 18-21 are withdrawn from further consideration as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 1-12 and 17 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Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.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 rejections of record set forth in the last Office action have been considered but are moot because they do not pertain to the new rejections necessitated by claim amendments set forth hereinbelow.
New Rejections Necessitated by Amendment
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 2-4 and 7-9 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 2 recites that the one or more ONT agents of claim 1 “comprise miRNA agomirs”. It is noted that claim 1 as currently amended already requires that the ONT “comprises a miR-515-3p agomir”, which is a narrower limitation than the “miRNA agomirs”. Hence, claim 2 fails to further limit the subject matter of claim 1.
Claim 3 recites that the one or more ONT agents of claim 1 are “14 to 25 nucleotides in length.” It is noted that SEQ ID NO:13 now recited and required by claim 1 is 22 nucleotides in length. Hence, the recitation of the shorter length (e.g., 14) than the 22-mer sequence fails to include all limitations of claim 1.
Claim 4 recites that the ONT agents of claim 1 comprise a “PNA” backbone. However, claim 1 as currently amended requires the presence of a “gPNA” backbone, which is a narrower limitation than the “PNA” backbone. Hence, claim 4 fails to further limit the subject matter of claim 1.
Claims 7-9 recite that the one or more targeting elements of claim 1 comprise a lipid. However, claim 1 as currently amended already requires that the targeting element comprises a specific type of lipid, “dotriacontahexaenoic acid”, which is a narrower limitation than the “lipid”. Hence, claims 7-9 fail 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 5-6 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 5-6 each recite “a miR-515-3p agomir”. It is unclear whether the agomir recited in claims 5-6 is meant to refer to the agomir already recited in claim 1 as currently amended, or whether the agomir of claims 5-6 is an additional agomir.
For examination purpose, the limitation recited in claims 5-6 will be interpreted as “the miR-515-3p agomir” of claim 1.
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.
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 1-12 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter) in view of Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Thibonnier 2021 teaches making a composition comprising oligonucleotides of “miR-515 agomir” and “miR-22 antagomir”, which are linked via a covalent bond linker or a disulfide bond linker to “dotriacontahexaenoic acid”, which delivers the oligonucleotides “to a targeted adipocyte” and are “naturally transported by fatty acid translocase”, wherein the agomir has the nucleic acid sequence of “hsa-miR-515-3p” and the antagomir inhibits “hsa-mir-22-3p”, wherein the oligonucleotides modulate “lipid oxidation”, wherein the oligonucleotides are modified with “peptide nucleic acid (PNA).” See paragraphs 0013-0015, 0018-0019, 0036, 0069, 0082, 0102-0103, 0108, 0113; claims 1-21.
Thibonnier 2021 does not disclose that the PNA is a gamma PNA, nor does Thibonnier disclose the nucleotide sequences of miR-515 agomir and miR-22 antagomir.
Vikram teaches that a “gPNA oligomer” comprising “g peptide nucleic acid (gPNA)” backbone “confers even stronger binding affinity for the target RNA than that of the classical PNAs” and forms a duplex with target RNA/DNA with “higher stability”, and the gPNAs provide “improved water solubility” thus increased “biocompatibility” hence are “effective tools in several biological and biomedical applications”, wherein a gPNA oligomer can be designed to target a miRNA. See abstract; paragraphs 0067-0070, 0106, and 0147.
Jakob discloses that hsa-miR-515-3p mimic sequence is 5’-GAGUGCCUUCUUUUGGAGCGUU, which is identified as SEQ ID NO:1 as shown below. See also paragraph 0017.
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It is noted Jakob’s SEQ ID NO:1 is 100% identical to SEQ ID NO:13 claimed in the instant case.
Thiobonnier 2019 teaches making an inhibitor (antagomir) of hsa-miR-22-3p, wherein the antagomir has the sequence of 5’-CTTCTTCAACTGGCAGCT, which is identified as SEQ ID NO:4 as shown below. See also paragraphs 0006, 0014, and 0018.
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It is noted SEQ ID NO:4 of Thiobonnier 2019 is 100% identical to SEQ ID NO:12 claimed in the instant case.
It would have been obvious to one of ordinary skill in the art before the effective filing date to incorporate gPNA backbone into the “miR-515 agomir” and “miR-22 antagomir” of Thibonnier 2021’s composition comprising dotriacontahexaenoic acid. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to improve the properties of the agomir and antagomir because the gPNA backbone was known to confer many advantageous properties such as improved “biocompatibility”, “higher stability”, and “even stronger binding affinity for the target RNA than that of the classical PNAs” thus are utilized as “effective tools” in “biomedical applications” as evidenced by the teachings of Vikram. It would also have been obvious to one of ordinary skill in the art to utilize the art-recognized miR-155-3p mimic sequence of SEQ ID NO:1 disclosed in Jakob and the art-recognized miR-22-3p antagomir sequence of SEQ ID NO:4 disclosed in Thiobonnier 2019 as the “miR-515 agomir” sequence and “miR-22 antagomir” sequence, respectively, when making the gPNA backbone-modified composition of Thibonnier 2021 because the nucleotide sequences providing the intended agomir/antagomir function were already available in the art.
In view of the foregoing, claims 1-12 and 17 taken as a whole would have been prima facie obvious before the effective filing date.
Double Patenting
The text of the judicially created doctrine not included in this action can be found in a prior Office action.
Claims 1-12 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 9,034,839 B2 in view of Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter), Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘839 patent claims that require a miRNA agent that is “an agomir of hsa-miR-515-3p” that “is linked to” a “targeting moiety”, which “delivers the miRNA agent to a specific cell type or tissue” including “adipocyte”, “hepatocyte”, and “myocyte”. It is noted that scope of the term “linked to” claimed in the ‘839 patent claims comprises a noncovalent “linker” including “a biotinsteptavin bridge” and the scope of the term “targeting moiety” claimed in the ‘839 patent claims reads on “lipid moieties such as a cholesterol moiety” as well as a moiety that binds to “FAT (CD36)” as disclosed in the ‘839 patent specification. Regarding claims 3-4, 6, 9, and 17, is was known in the art that the nucleotide sequence of miR-515-3p mimic is a 22-mer of SEQ ID NO:13 claimed in the instant case as evidenced by the disclosure of Jakob (see SEQ ID NO:1) and furthermore, it was known in the art that dotriacontahexaenoic acid is a fatty acid that is known to deliver a PNA-modified agomir “to a targeted adipocyte” and “is naturally transported by fatty acid translocase”, wherein the fatty acid can be linked to the agoamir via a disulfide bond linker as taught by Thibonnier 2021, who also taught that “hsa-miR-515-3p” modulates “lipid oxidation”. It would have been obvious to further include miR-22-3p antagomir having SEQ ID NO:12 claimed in the instant case in the “miRNA agent” of the ‘839 patent claims in order to further modulate thermogenesis because it was known in the art that “administration of a mir-22 inhibitor to a subject increases thermogenesis” as evidenced by paragraph 0006 of Thibonnier 2019, who also disclosed SEQ ID NO:4 (identical to SEQ ID NO:12 of the instant claims) as the miR-22-3p inhibitor (antagomir) sequence. It would have been obvious to incorporate gPNA backbone to the agomir and antagomir for improved properties in view of the teachings of Vickram described in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1-12 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9,453,224 B2 in view of Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter), Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘224 patent claims that require an “antagomir” of “miR-22-3p” that “is linked to” a “targeting moiety”, which “delivers the miRNA agent to a specific cell type or tissue” including “subcutaneous adipose tissue”, wherein the miRNA agent modulates mitochondrial activity. It is noted that scope of the term “linked to” claimed in the ‘224 patent claims comprises a noncovalent “linker” including “a biotinsteptavin bridge” and the scope of the term “targeting moiety” claimed in the ‘224 patent claims reads on “lipid moieties” as well as a moiety that binds to “FAT (CD36)” as disclosed in the ‘224 patent specification. It would have been obvious to further include an agomir of miR-155-3p when practicing the method of ‘224 patent claims because “miR-515 agomirs” were taught to have the same function/activity as “miR-22 antagomirs” in modulating thermogenesis as evidenced by the teachings of Thibonnier 2021 (see paragraphs 0109 and 0113), who also taught using dotriacontahexaenoic acid as the lipid-based targeting moiety. The obviousness of SEQ ID NO:12 for the antagomir, SEQ ID NO:13 for the agomir, and gPNA backbone so as to arrive at the instant claims is found in the teachings of Vickram, Jakob, and Thibonnier 2019 as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1-12 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 9,803,203 B2 in view of Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter), Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘203 patent claims that require an “antagomir” of miR-22 that “is linked to a targeting moiety”, which “delivers the miRNA agent to a specific cell type, organ or tissue”, wherein the antagomir modulates mitochondrial activity. It is noted that scope of the term “linked to” claimed in the ‘203 patent claims comprises a noncovalent “linker” including “a biotinsteptavin bridge” in view of the ‘203 patent specification; the scope of the term “targeting moiety” claimed in the ‘203 patent claims reads on “lipid moieties” as well as a moiety that binds to “FAT (CD36)” as disclosed in the ‘203 patent specification; and the scope of the “specific cell type” claimed in the ‘203 patent claims is defined to read on “adipocytes” as disclosed in the ‘203 patent specification. It would have been obvious to further include an agomir of miR-155-3p when practicing the method of ‘203 patent claims because “miR-515 agomirs” were taught to have the same function/activity as “miR-22 antagomirs” in treatment of obesity/type 2 diabetes mellitus as evidenced by the teachings of Thibonnier 2021, who also taught using dotriacontahexaenoic acid as the lipid-based targeting moiety. The obviousness of SEQ ID NO:12 for the antagomir, SEQ ID NO:13 for the agomir, and gPNA backbone so as to arrive at the instant claims is found in the teachings of Vickram, Jakob, and Thibonnier 2019 as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1-12 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,253,319 B2 in view of Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter), Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘319 patent claims that require an “antagomir” miR-22-3p comprising “peptide nucleic acid modification”, “wherein the antagomir is linked to a targeting moiety that specifically binds to CD36/Fatty Acid Transporter (FAT/SR-B2)”, which “delivers the antagomir to adipose tissue.” It is noted that scope of the term “linked to” claimed in the ‘319 patent claims comprises a noncovalent “linker” including “a biotinsteptavin bridge” in view of the ‘319 patent specification and the scope of the term “targeting moiety” claimed in the ‘319 patent claims reads on “lipid moieties” as disclosed in the ‘319 patent specification. It would have been obvious to further include an agomir of miR-155-3p when practicing the method of ‘319 patent claims because “miR-515 agomirs” were taught to have the same function/activity as “miR-22 antagomirs” in modulating thermogenesis as evidenced by the teachings of Thibonnier 2021 (see paragraphs 0109 and 0113), who also taught using dotriacontahexaenoic acid as the lipid-based targeting moiety. The obviousness of SEQ ID NO:12 for the antagomir, SEQ ID NO:13 for the agomir, and gPNA backbone so as to arrive at the instant claims is found in the teachings of Vickram, Jakob, and Thibonnier 2019 as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1-12 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,690,804 B2 as evidenced by Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter), Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘804 patent claims that require to a therapeutic agent comprising “miR-515 agomir” and “miR-22 antagomir” linked/conjugated via a covalent bond linker to a fatty acid, which is “dotriacontahexaenoic acid”, which “specifically binds to Fatty Acid Translocase” and has the function of “facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte”, wherein the therapeutic agent modulates lipid oxidation. It is noted that the ‘804 patent specification discloses that “hsa-miR-515-3p” is used in the method. It would have been prima facie apparent that the 22-mer miR-515 agomir that is miR-515-3p used in the ‘804 patent claims has SEQ ID NO:13 claimed in the instant case in view of the art-recognized fact that miR-515-3p has the sequence of SEQ ID NO:13 as evidenced by Jakob’s SEQ ID NO:1, and similarly, the miR-22 antagomir has SEQ ID NO:12 claimed in the instant case in view of the disclosure of Thiobonnier 2019. It would have been obvious to modify the “miR-515 agomir” and “miR-22 antagomir” of the ‘804 patent claims with gPNA backbone because making a PNA-modified agomir/antagomir was already known in the art as taught by Thibonnier 2021, wherein gPNA backbone-containing oligonucleotides were known to confer advantages as taught by Vikram, whose teachings are described in the §103 rejection above, which is fully incorporated by reference thus will not be repeated.
Claims 1-12 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3 and 7-9 of U.S. Patent No. 12,286,625 B2 in view of Thibonnier (US 2021/0145745 A1, of record), Vikram et al. (US 2023/0322862 A1), and Jakob et al. (US 2023/0242911 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘625 patent claims drawn to a method that requires miR-22 antagonist of SEQ ID NO:4 (identical to SEQ ID NO:12 claimed in the instant case) conjugated to a fatty acid, which is “dotriacontahexaenoic acid.” It would have been obvious to further include an agomir of miR-155-3p when practicing the method of ‘625 patent claims because “miR-515 agomirs” were taught to have the same function/activity as “miR-22 antagomirs” in modulating thermogenesis as evidenced by the teachings of Thibonnier (see paragraphs 0109 and 0113). The obviousness of SEQ ID NO:13 for the agomir and gPNA backbone so as to arrive at the instant claims is found in the teachings of Vickram and Jakob as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 1-12 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 16-24 of copending Application No. 17/656,901 in view of Thibonnier (US 2021/0145745 A1, of record; “Thibonnier 2021” hereinafter), Vikram et al. (US 2023/0322862 A1), Jakob et al. (US 2023/0242911 A1, of record), and Thibonnier (US 2019/0127736 A1; “Thibonnier 2019” hereinafter).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by and overlap in scope with the ‘901 claims that are drawn to a therapeutic agent of “miRNA oligonucleotide therapeutic” that is miRNA “agomir” and “antagomir” linked via a covalent bond linker to “dotriacontahexaenoic acid” that “binds to Fatty Acid Translocase” and also binds to “an adipocyte.” It would have been obvious to use an miR-155 agomir and an miR-22 antagomir for the agomir/antagomir claimed in the ‘901 claims because the miR-155 agaomir and the miR-22 antagomir were known to be differentiation regulators of adipocytes, which are the target of the agomir/antagomir of the ‘901 claims, as evidenced by the teachings of Thibonnier 2021. The obviousness of SEQ ID NO:12 for the antagomir, SEQ ID NO:13 for the agomir, and gPNA backbone so as to arrive at the instant claims is found in the teachings of Vickram, Jakob, and Thibonnier 2019 as explained in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
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.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
