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/Application
The claims filed on 06/25/2026 is acknowledged. Claims 1, 5, and 10 are amended. Claims 4, 7, and 8 are canceled. Claims 1 – 3, 5, 6, and 9 – 24 are currently pending.
Election/Restrictions
Applicant’s election of Group I, claims 1 – 3, 5, 6, and 9 – 11, drawn to a compound of Formula I, an oligonucleotide primer for RNA capping; and Applicant’s election of species of compound 1 in the reply filed on 06/25/2026 is acknowledged.
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Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 12 – 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II and Group III, there being no allowable generic or linking claim.
In searching for the elected species, art reading on “Y1 and Y2 together form an LNA ring” was identified. Thus, the search has been expanded to include compounds 3 and 5 in claim 10.
Claims 1 – 3, 5, 6, and 9 – 11 are examined on the merits herein.
Priority
The instant application is a National Stage Application of PCT/KR2021/014625 filed 10/19/2021, and claims foreign priority to KR10-2020-0135823 filed on 10/20/2020. The certified copy has been filed in the instant application on 04/18/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted in the instant application
on 04/18/2023, 10/28/2024, 02/13/2025, and 10/10/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 1 – 3, 5, 6, and 9 – 11 are rejected under 35 U.S.C. 103 as being unpatentable over Sikorski et al (The identity and methylation status of the first transcribed nucleotide in eukaryotic mRNA 5’ cap modulates protein expression in living cells, Nucleic Acids Research, 2020, Vol. 48, No. 4, 1607 – 1626) (IDS 04/18/2023) in view of US 2020/0040026 (IDS 04/18/2023).
Sikorski teaches that 7-methylguanosine 5’ cap on mRNA is necessary for efficient protein expression in vitro and in vivo and teaches trinucleotide 5’ cap analogs (m7GpppN(m)pG), which are utilized by RNA polymerase T7 to initiate transcription from templates carrying ф6.5 promoter and enable production of mRNAs differing in
the identity of the first transcribed nucleotide (N = A, m6A, G, C, U) and its methylation status (±2’-O-methylation) (Abstract).
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Sikorski teaches the structures of trinucleotide cap analogs synthesized in Figure 1 shown above (pg. 1609). Sikorski specifically teaches the trinucleotide cap analog, m7GpppAmpG (2). Sikorski teaches how efficiently the trinucleotide cap
analogs were incorporated into RNA during in vitro transcription (IVT) with the highest
capping efficiency was observed for trinucleotides featuring a purine nucleotides at the position of the first transcribed nucleotide (‘purine trinucleotides’): m7GpppAmpG (90%),
m7GpppApG (89%), m7GpppGmpG (86%), m7GpppGpG (80%), while the lowest capping efficiencies were observed for pyrimidine trinucleotides: m7GpppUmpG (56%), m7GpppUpG (56%), m7GpppCmpG (54%) and m7GpppCpG (60%), comparable to the capping efficiencies obtained for m7GpppG (69%) and m2 7,3’-OGpppG (56%).
The teachings of Sikorski differ from the instantly claimed invention in that Sikorski does not teach a 2’-fluoro-2’-deoxy-adenosine or LNA-ribose modification in adenosine in the cap1 (Am) position of the trinucleotide analog m7GpppAmpG (2).
US’026 teaches a trinucleotide cap analog comprising m7G(5′)p3-N1pN2 for increased efficiency of in vitro transcription of m7G(5′)p3-RNA, wherein the trinucleotide cap analog increases the efficiency of in vitro transcription (Abstract).
US’026 teaches a compound of formula m7G(5′)ppp-N1pN2, wherein m7G is a ribonucleotide consisting of N7-methylguanine and a ribose, wherein ppp is a 5′ to 5′ triphosphate linkage; wherein N1 and N2 are ribonucleotides, wherein one or both of N1 and N2 ribonucleotides consist of a base selected from adenine, uracil, cytosine, or guanine; and a bicyclic (LNA) ribose, a seco (UNA) ribose, or a modified ribose wherein one or both of the ribose 2′ or 3′ carbons has a fluoro or a C1-C6 alkoxy substituent; and wherein the m7G ribonucleotide is linked at its 5′-OH to the triphosphate bridge, wherein the triphosphate bridge is linked to a 5′-OH of the N1 ribonucleotide wherein N1 nucleotide is linked via its 3′-OH to a phosphate, p, wherein the phosphate is linked to a 5′-OH of the N2 ribonucleotide; or a salt or solvated form thereof (pg. 4, col. 2, [0069]). A compound of formula m7G(5′)p3(5′)N1pN2 is wherein N1 is a ribonucleotide consisting of adenine, uridine, guanine, or cytidine, preferably adenine (pg. , col. , [0056]). A compound of formula m7G(5′)p3(5′)N1pN2 is wherein N1 consists of a LNA, a UNA, or a ribose wherein one or both of the ribose 2′ or 3′ carbons has a fluoro or a C1-C6 alkoxy substituent (pg. 4, col. 1, [0059]). A compound of formula m7G(5′)p3(5′)N1pN2 is wherein N2 is a ribonucleotide consisting of adenine, uridine, guanine, or cytidine, preferably guanine (pg. 4, col. 1, [0060]). US’026 exemplifies the synthesis of 2′-O,4′-C-methylene-linked bicyclic guanine nucleotide (compound 32, FIG. 10) in Example 9 (pg. 11, col. 2, [0144]), and dinucleotide m62′OMeAp-locked-2′OMeG (compound 35, FIG. 11) in Example 10 (pg. 12, col. 1, [0153]), and trinucleotide cap analog, m7G(5′)pppm62′OMeAp-locked-2′-OMeG (compound 36, FIG. 12) in Example 11 (pg. 12, col. 2, [0155]).
It would have been obvious to combine Sikorski and US’026 before the effective filing date of the instantly claimed invention by incorporating the 2’-fluoro-2’-deoxy-ribose modification or the LNA-ribose modification in the N1 nucleotide as taught by US’026 to the trinucleotide cap analog m7GpppAmpG (2) of Sikorski to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the sugar in the cap1 (Am) nucleotide of the cap analog of Sikorski to 2’-fluoro-adenosine or locked-adenosine and have a reasonable expectation of success as US’206 teaches the synthesis of trinucleotide cap analogs for improved in vitro mRNA synthesis and translation of m7G(5’)p3-RNA and teaches the synthesis of 2′-O,4′-C-methylene-linked bicyclic guanine nucleotide (compound 32, FIG. 10) in Example 9 (pg. 11, col. 2, [0144]), and dinucleotide m62′OMeAp-locked-2′OMeG (compound 35, FIG. 11) in Example 10 (pg. 12, col. 1, [0153]), and trinucleotide cap analog, m7G(5′)pppm62′OMeAp-locked-2′-OMeG (compound 36, FIG. 12) in Example 11 (pg. 12, col. 2, [0155]).
Regarding claim 10, Sikorski’s m7GpppAmpG (2) differs from the instantly elected species only in that 2’-methoxy modification is taught in Am instead of 2’-fluoro. It would have been prima facie obvious for one of ordinary skill in the art to synthesize 2’-fluoro-2’-deoxy-adenosine as US’026 teaches a compound of formula m7G(5′)p3(5′)N1pN2 is wherein N1 consists of a LNA, a UNA, or a ribose wherein one or both of the ribose 2′ or 3′ carbons has a fluoro or a C1-C6 alkoxy substituent (pg. 4, col. 1, [0059]). It would have been prima facie obvious for one of ordinary skill in the art to synthesize compounds 3 and 5 in the instant claim as US’026 teaches the synthesis of 2′-O,4′-C-methylene-linked bicyclic guanine nucleotide (compound 32, FIG. 10) in Example 9 (pg. 11, col. 2, [0144]), and dinucleotide m62′OMeAp-locked-2′OMeG (compound 35, FIG. 11) in Example 10 (pg. 12, col. 1, [0153]), and trinucleotide cap analog, m7G(5′)pppm62′OMeAp-locked-2′-OMeG (compound 36, FIG. 12) in Example 11 (pg. 12, col. 2, [0155]). One of ordinary skill in the art would have reasonable expectation of success as the structures of the instantly claimed invention can be envisioned by the combination of the teachings of Sikorski and US’026 as it is combining prior art elements according to known methods to yield predictable results, namely efficient oligonucleotide cap analogs (See MPEP 2143(I)(A)).
Conclusion
Claims 1 – 3, 5, 6, and 9 – 11 are rejected. No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANAKI ANANTH MAHADEVAN whose telephone number is (571)272-0230. The examiner can normally be reached Monday-Friday 8-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at 5712705241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.A.M./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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