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 preliminary amendment dated 12/29/2023, claims 4-22 are amended. No claims are newly added or canceled.
Claims 1-22 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/JP2022/026411, filed on 6/30/2022. The instant application claims foreign priority to JP 2021-109239 filed on 6/30/2021 and JP 2021-169846 filed on 10/15/2021. Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d). The certified copy has been filed in the instant application on 12/29/2023.
Information Disclosure Statement
The information disclosure statements (IDS) dated 12/29/2023, 4/30/2025 and 4/29/2026 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609, except where noted. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
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 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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-12, 14 and 16-22 are rejected under 35 U.S.C. 103 as being unpatentable over Wiederholt et al. (US 2003/0083272A1, IDS).
Wiederholt discloses an mRNA polynucleotide comprising at least one chemical modification. (Claim 1) Wiederholt depicts the modified mRNA, comprising a 5’ UTR, a coding region, a 3’UTR and a poly(A) tail, as follows: (Figure 1)
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Wiederholt further teaches that:
The phosphodiester bonds of the poly A tail may be fully substituted with phosphothioate bonds, where a fully substituted poly(A) tail necessarily includes the first, second, third, fourth and fifth nucleotides from the 3’ end of the poly(A) tail; (Figure 4; ¶0160, 0163)
The poly(A) tail may have a length of 50-500 nucleotides; (Claim 10; ¶0112)
Additionally or alternatively, the normal 2'-O-methyl modification of the nucleoside sugar could be changed to the myriad of 2' modified analogs known in the art (for example, 2'-O-ethyl, propyl, methoxyethoxy, allyl, or 2'F, or 2' amino); (¶0105)
Phosphorothioate linkages, or other stabilizing modifications of RNA, may be incorporated into a poly A tail to add further stabilization to an mRNA molecule. Such modified poly A tails may be added to sense mRNA molecules using poly A polymerase. In yet another embodiment, other, more drastically modified, analogs of A or other bases can be incorporated into a poly A tail (e.g., 2'-0-methyl or methylphosphonate modified). In one embodiment of the invention, other modifications may be made downstream of the poly A tail in order to retain the poly A binding sites and further block 3' exonucleases. (¶0111)
Modified sense mRNA may comprise: DNA containing mRNA (diguanosine Cap:5' UTR (modified or unmodified), coding region(modified or unmodified:3' UTR (modified or unmodified), poly A tail (modified or unmodified), DNA containing end block (for example phosphorothioate DNA, methylphosphonate DNA); (¶0142-0143)
An mRNA molecule may be altered by including substituted purines or related analogs to increase resistance to nucleases; (¶0125)
The coding region of an mRNA molecule to be stabilized is between about 7000 and 8000 nucleotides; (¶0053)
Wiederholt does not exemplify of claim that the poly(a) tail comprises 65% or more sugar modified adenosines.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that at least one poly A nucleoside sugar could be modified to bear a 2’-O-methyl, 2'-O-ethyl, propyl, methoxyethoxy, allyl, or 2'F, or 2' amino, preferably a 2’-O-methyl group, because Wiederholt specifically suggests such modifications stabilize mRNA. It would be further obvious that the nucleoside sugars in the poly A tail of Wiederholt could be modified to have 2’ substituent as listed above, in a range of at least one modified nucleoside sugar to all poly A nucleoside sugars (i.e. 100% of the poly A nucleoside sugars are modified), thereby arriving at the instant invention, because Wiederholt teaches that all phosphodiester bonds in the poly A tail may be replaced with phosphothioate linkages. Thus, Wiederholt envisions chemical modification of all nucleosides in the poly A tail, which in combination with the teaching that at least one nucleoside sugar may be modified, reasonably extends to envisioning all nucleoside sugars in the poly A tail being modified.
With respect to claim 8 and the range of the poly A tail being 2-40 bases, the disclosure of Wiederholt that the poly A tail may be 50 bases, while not explicitly overlapping the instant range, is considered sufficiently close to the instantly claimed range such that absent evidence to the contrary, one of ordinary skill in the art would reasonably expect the prior art mRNA to have similar properties to the instant claims. It is held that a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (MPEP § 2144.05)
Accordingly, the instant claims are prima facie obvious over the teachings of the prior art.
Claims 9, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Wiederholt et al. (US 2003/0083272A1, IDS), in view of Miyamoto et al. (US 2013/0196331A1, PTO-892).
The disclosure of Wiederholt is referenced as discussed above. Wiederholt does not teach spacer structures.
Miyamoto et al. discloses that mRNA may be modified by inserting a PEG spacer region between the 5’UTR and the coding region. (¶0067-0071)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that, in view of what is known in the art as per Miyamoto, that the 5’UTR of Wiederholt could be modified to include a PEG spacer, thereby arriving at the instant invention.
Accordingly, the instant claims are prima facie obvious over the teachings of the prior art.
Claims 15 is rejected under 35 U.S.C. 103 as being unpatentable over Wiederholt et al. (US 2003/0083272A1, IDS), in view of Chen et al. (WO 2012/138453, IDS).
The disclosure of Wiederholt is referenced as discussed above. Wiederholt does not teach the structure of claim 15.
Chen discloses modified RNA where a known base modification is N6-methyladenosine (m6A). (Claim 14)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that, in view of what is known in the art as per Chen, in combination with the teaching of Wiederholt that mRNA may be modified by base modifications, that the base modifications of Wiederholt could be extended to include N6-methyladenosine (m6A), thereby arriving at the instant invention.
Accordingly, the instant claims are prima facie obvious over the teachings of the prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DALE R MILLER whose telephone number is (571) 272-6146. The examiner can normally be reached on M-F 7:00 AM – 3:30 PM EST.
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/DALE R MILLER/Primary Examiner, Art Unit 1693
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