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 Claims
Claims 1-20 are currently pending and under examination on the merits in the instant application.
Drawings
The drawings are objected to because they contain Figures that are not in black colored font, thereby rendering the non-black color texts not clearly legible. See for instance Figure 1B and 2A. Note that the patent application content should be in black font for legibility. That is, all application papers must be clearly legible using black colored font text and black lines. See MPEP §608.01. In addition to the illegibility issues, some of the Figures contain undisguisable legends. That is, different legends are not clearly distinguishable from each other thus the different bars in the graph are not clearly identifiable. See for instance Figures 4B and 5B. Applicant is required to review all Figures and make appropriate corrections for clear legibility and clear distinction for different legends.
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 § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 6-7, 9-12, and 14-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Moulton et al. (WO 2021/226485 A2, applicant’s citation).
Moulton teaches making a pharmaceutical composition comprising a pharmaceutically acceptable carrier such as liposomes and an antisense oligonucleotide of SEQ ID NO:2 (5’-CCTGGGAAGGTATAAACCTTTAAT) that is administered to a subject for treatment of SARS-CoV-2 infection, wherein the oligonucleotide can be modified with “phosphorodiamidate morpholino (PMO)”, “2’-O-methyl phosphorothioate (2’-OMePS)”, or “locked nucleic acid (LNA)”. See claims 1-10, 23, and 33-36; pages 15-18 and 21-23.
Since Moulton’s antisense oligonucleotide sequence is 100% identical to SEQ ID NO:2 claimed in the instant case that is encompassed by claim 1, it necessarily follows that Moulton’s oligonucleotide would necessarily and inherently result in reduced SARS-CoV-2 RNA translation and increased SARS-CoV-2 RNA degradation in cells of the subject administered with Moulton’s oligonucleotide, absent objective evidence to the contrary.
Accordingly, claims 1-3, 6-7, 9-12, and 14-20 are described by Moulton et al.
Claims 1-3, 6-7, 11-12, 14-16, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vora et al. (bioRxiv, 10.1101/2021.09.09.459641, posted on September 9, 2021).
Vora discloses “locked nucleic acid antisense oligonucleotides (ASOs)” targeting “SARS-CoV-2 5’ UTR”, wherein the ASOs, in particular “ASO7”. can be used as a therapeutic agent for treating a subject having COVID-19 infection by suppressing viral translation, wherein “ASO7” has the nucleotide sequence of 5’-GTTACCTGGGAAGGTATAAACCTTTAAT. See pages 1-5; Figure 4A.
Since Vora’s ASO7 sequence is 100% identical to SEQ ID NO:4 claimed in the instant case that is encompassed by claim 1, it necessarily follows that Vora’s oligonucleotide would necessarily and inherently result in reduced SARS-CoV-2 RNA translation and increased SARS-CoV-2 RNA degradation in cells of the COVID-19-infected subject when treated with Vora’s oligonucleotide, absent objective evidence to the contrary.
Accordingly, claims 1-3, 6-7, 11-12, 14-16, and 18-20 are described by Vora et al.
Claims 1-4, 6-7, 9-12, 14-16, and 18-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Freier et al. (US 2023/0151366 A1).
Freier discloses a fully phosphorothioate and 2’-MOE modified antisense oligonucleotide of SEQ ID NO:511 (5’-TGGTTTGTTACCTGGGAAGG) targeting SARS-CoV-2. See paragraph 0141; Table 3.
It is noted that Freier’s SEQ ID NO:511 comprises the entire sequence of SEQ ID NO:3 claimed in the instant case.
Freier teaches that the antisense oligonucleotide can comprise LNA modifications. See paragraph 0289.
Freier teaches that the antisense oligonucleotide is formulated as a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is administered to a subject for treating SARS-CoV-2 infection. See paragraphs 0002 and 0347-0350.
Since Freier’s antisense oligonucleotide sequence fully satisfies the structural limitations set forth in claim 1, it necessarily follows that Freier’s oligonucleotide would necessarily and inherently result in reduced SARS-CoV-2 RNA translation and increased SARS-CoV-2 RNA degradation in cells of the COVID-19-infected subject when treated with Freier’s oligonucleotide, absent objective evidence to the contrary.
Accordingly, claims 1-4, 6-7, 9-12, 14-16, and 18-20 are described by Freier et al.
Claims 1, 3-12, 15-16, and 18-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Naar et al. (US 2024/0102015 A1).
Naar discloses LNA mixmer antisense oligonucleotides targeting the 5’-leader (5’ UTR) of SARS-CoV-2, for instance, “anti-5’ leader LNA” “ASO#29” (or “CRM0533”), which significantly inhibited the expression level of the virus, wherein “ASO#29” (or “CRM0533”) targets 5’-UUCCCAGGUAACAAAC (SEQ ID NO:153) and has the sequence of 5’-GTtTgTtACcTgggAA, wherein the upper case letters represent LNA and the lower case letters represent DNA, wherein the ASO comprises phosphorothioate linkages. See Figure 1b; Extended Data Table 1; Table 4.
It is noted that the target sequence of Naar’s “ASO#29” (or “CRM0533”) corresponds to the RNA counterpart of positions 17-32 of SEQ ID NO:1 claimed in the instant case.
Naar teaches that “the LNA modification” comprises “a methylene bridge connecting 2’-oxygen and 4’-carbon of ribose” and the disclosed LNA ASOs can be formulated as a pharmaceutical composition further comprising a pharmaceutically acceptable carrier/excipient, wherein the pharmaceutical composition is administered to a subject having COVID-19 infection “for the method of treating COVID-19”. See paragraphs 0005 and 0027.
Since Naar’s “ASO#29” (or “CRM0533”) sequence fully satisfies the structural limitations set forth in claim 1, it necessarily follows that Naar’s oligonucleotide would necessarily and inherently result in reduced SARS-CoV-2 RNA translation and increased SARS-CoV-2 RNA degradation in cells of the COVID-19-infected subject when treated with Naar’s oligonucleotide, absent objective evidence to the contrary.
Accordingly, claims 1, 3-12, 15-16, and 18-20 are described by Naar et al.
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 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Moulton et al. (WO 2021/226485 A2, applicant’s citation) in view of van Rooij et al. (US 2013/0344135 A1).
Moulton teaches making a pharmaceutical composition comprising a pharmaceutically acceptable carrier such as liposomes and an antisense oligonucleotide of SEQ ID NO:2 (5’-CCTGGGAAGGTATAAACCTTTAAT) that is administered to a subject for treatment of SARS-CoV-2 infection, wherein the oligonucleotide can be modified with “phosphorodiamidate morpholino (PMO)”, “2’-O-methyl phosphorothioate (2’-OMePS)”, or “locked nucleic acid (LNA)”. See claims 1-10, 23, and 33-36; pages 15-18 and 21-23.
Moulton does not expressly teach that the LNA-containing oligonucleotide has at least 40% LNA, at least 40% DNA, or at least 40% RNA.
van Rooij teaches that LNA(L)-DNA(D) mixmer antisense oligonucleotides can have various modification patterns such as the following disclosed in Figure 1A:
LDLDLLDLDLDLDLLD (M-10679)
LDDLLDLDLLDLDLDL (M-10683)
LDLLDDLLDLDLDLDL (M-11184)
LDLDLDLLDLDLDLDL (M-11298)
LDDLLDLLDLDLDLDL (M-11299)
LLDDLDLDLLDLDLDL (M-11300)
van Rooij teaches that the “fully phosphorothioate-linked” LNA mixmer modification motifs/patterns “provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.” See abstract; paragraph 0013.
It would have been obvious to one of ordinary skill in the art before the effective filing date to utilize the art-recognized mixmer modification motifs/patterns of van Rooij and incorporate the motifs/patterns into the 24-mer antisense oligonucleotide sequence of Moulton. 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 potency, efficiency of delivery, target specificity, toxicity, and/or stability of Moulton’s SARS-CoV-2-targeting antisense oligonucleotide, thereby improving the therapeutic efficacy of the oligonucleotide because the “fully phosphorothioate-linked” LNA-DNA mixmer motifs/patterns of van Rooij were taught to “provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.”
Accordingly, claims 1-12 and 14-20 taken as a whole would have been prima facie obvious before the effective filing date.
Claim Objections
Claim 13 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form.
Conclusion
Claims 1-12 and 14-20 are rejected.
Claim 13 is objected to.
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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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.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
