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 .
DETAILED ACTION
Pursuant to the amendment dated 07/02/2026, claims 20-25 were amended. Claims 1-25 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/JP2022/026665 filed 07/05/2022 which claims foreign priority to JAPAN 2021-111420 filed on 07/05/2021.
Information Disclosure Statement
The information disclosure statements (IDS) dated 01/04/2024, 08/05/2025, 01/08/2026, and 09/03/2026 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
Election/Restrictions
Applicants’ election with traverse of the invention of Group IV, claims 20-24, drawn to an mRNA drug comprising a hydrophobic nucleotide-based substance comprising a hydrophobic protecting group P1 or P2, in the reply filed on 07/02/2026 is acknowledged.
The traversal is on the ground(s) that the International Searching Authority, examining a similar set of claims, found Unity of Invention to be present in the international application of which the present application is a national stage entry under 35 U.S.C. § 371. As stated in the MPEP, "it is clear that the decision with respect to unity of invention rests with the International Searching Authority or the International Preliminary Examining Authority". MPEP § 1850. This is not found persuasive because MPEP § 1893.03(d) and 37 C.F.R. 1.499 states that “If the examiner finds that a national stage application lacks unity of invention under § 1.475, the examiner may in an Office action require the applicant in the response to that action to elect the invention to which the claims shall be restricted. Such requirement may be made before any action on the merits but may be made at any time before the final action at the discretion of the examiner.” Groups I-IV lack unity of invention because even though the inventions of these groups require the technical feature of a hydrophobic nucleotide-based substance comprising a hydrophobic protecting group P1 or P2, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Litosh et al. (Nucleic Acids Research, published 01/11/2011, see IDS dated 01/04/2024).
Litosh is drawn to 3’-OH unblocked reversible terminator. Litosh exemplifies a series of 5-(2-nitrobenzyloxy)methyl-dUTP analogs with photochemically cleavable terminators (abstract). Litosh exemplifies hydrophobic protecting groups that meet the limitations of P1 when R2 and R3 are hydrogens, and R1 and R4 are methyl groups (Figure 1, page 4). Litosh teaches that the triphosphates were purified by Q Sepharose FF anion-exchange chromatography followed by RP-HPLC (page 5).
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5-(2-nitrobenzyloxy)methyl-dUTP analog dU.IV (Figure 1, page 4).
Therefore, as shown above, no special technical feature exists for the different species as defined by PCT Rule 13.2 because the hydrophobic nucleotide-based substance comprising a hydrophobic protecting group P1 or P2 does not make a contribution over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-19 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Groups I-III, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/02/2026.
Claims 20-24 are examined on the merits.
Drawings
The drawings are objected to because in Figures 1-10, 39, 40, and 45 the axes, labels, and structures are illegible. In Figures 24, 26, 32, 37, 38, 42, 43 and 44 the structures are illegible. 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.
Specification
The disclosure is objected to because of the following informalities: Drawings of Chemical Formula 10 (page 10), Chemical Formula 23 (page 20), Chemical Formula 26 (page 33), Chemical Formula 29 (page 37), Chemical Formula 32 (page 42), Chemical Formula 36 (page 48), Chemical Formula 40 (page 55), Chemical Formula 44 (page 62), Chemical formula 48 (page 64), Chemical Formula 54 (page 79), Chemical Formula 55 (page 83), Chemical Formula 58 (page 92), Chemical Formula 60( page 99), Chemical Formula 61 (page 112), Chemical Formula 70 (page 121), Chemical Formula 71 (page 125), Chemical Formula 74 (page 133), Chemical Formula 75 (page 141), Chemical Formulas 76-77 (page 148), Chemical Formulas 78-79 (page 156), Chemical Formula 80 (page 162), Chemical Formula 84 (page 165), Chemical Formulas 86-89 (pages 170-171), Chemical Formulas 90-91 (page 173), Chemical Formula 92 (page 175), Chemical Formula 93 (page 177), Chemical Formula 94 (page 178), Chemical Formula 95 (page 180), Chemical Formula 96 (page 181), Chemical Formula 97 (page 182), Chemical Formula 98 (page 183), Chemical Formula 99 (page 184), Chemical Formula 100 (page 185), Chemical Formula 101 (page 187) ,Chemical Formula 102 (page 188), Chemical Formula 103 (page 189), and Chemical Formula 104 (page 190) are illegible.
Appropriate correction is required.
Claim Objections
Claim 22 is objected to because of the following informalities: Figures EC5-EC12 are not legible. 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.
Claims 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Chakraborty et al. (US 2014/0147454 A1, published 05/29/2014, PTO-892) and Saneyoshi et al. (Org. Let., published 07/14/2020, IDS dated 09/03/2026).
Chakraborty is drawn to compositions comprising terminally modified RNA molecules (abstract). Chakraborty discloses a 5’ cap structure of a modified nucleotide, CAP-021, and teaches a hydrophobic protecting group R1 that is CH2C6H4-NO2 (p-nitrobenzyl) and R2 is H (paragraph 0257 and Table 1). CAP-021 contains an mRNA substituent which would meet the limitation of the two additional nucleotides in E10. Chakraborty teaches that the 5’ cap analogs may be synthesized.
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CAP-021
Chakraborty’s CAP-021 does not teach the limitation of the hydrophobic protecting group P2 wherein the instant R1 represents a linear or branched alkyl group having 1 to 30 carbons atoms.
Saneyoshi is drawn to the development of labile protecting groups for the 2’ hydroxy group of RNA (title). Saneyoshi teaches a method for synthesizing phosphoramidites bearing reduction-activated protecting groups for bio-reversible RNAs that shows a protecting group introduction step of introducing the hydrophobic protecting group represented by the formula P2 into the nucleotide-based substance (Scheme 1, page 6007). Saneyoshi discloses a protecting group R1 that is the same as Chakraborty protecting group and also discloses a protecting group (R4) that meets all the limitations of the instant P2 wherein the instant R2, R3, R5, and R6 are hydrogens, and instant R1 and R4 are alkyl -CH3 groups. Saneyoshi teaches that permanent protection such as the 2’-OMe modification improves chemical stability and nuclease resistance; however, in some cases, this approach reduces the biological activity of the modified siRNAs (page 6006). Saneyoshi teaches that the attachment of electron donating groups to the benzene ring or benzylic carbon enabled fast and controllable deprotection of the 2’-hydroxyl protecting group under physiological conditions (abstract).
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It would have been prima facie obvious to combine the teachings of Chakraborty, and Saneyoshi before the effective filing date of the claimed invention by substituting the R1 p-Nitrobenzyl group on the CAP-021 compound taught by Chakraborty to be the R4 group in the protecting method taught by Saneyoshi to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to substitute the R1 p-Nitrobenzyl group on the CAP-021 compound taught by Chakraborty to be the R4 group taught by Saneyoshi because Saneyoshi teaches that the R4 protective group improves chemical stability and nuclease resistance. One of ordinary skill in the art would have a reasonable expectation of success because Chakraborty teaches a compound, CAP-021, that meets the limitation of E10 and P2 with the exception of the instant R1 group and Saneyoshi teaches the method of a protecting group introduction step of introducing the hydrophobic protecting group represented by the formula P2 into the nucleotide-based substance.
Conclusion
No claims allowed.
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/S.L.S./ Examiner, Art Unit 1693
/SCARLETT Y GOON/ Supervisory Patent Examiner, Art Unit 1693
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