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 the Claims
Claims 1-14 are pending in the application.
Claim 7-14 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected a device and method(s), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 5, 2025.
Claims 1-6 are now under consideration.
Election/Restriction
Applicant's election with traverse of claims 1-6 in the reply filed on December 5, 2025 is acknowledged. The traversal is on the grounds that a search for any group will necessarily produce results applicable for examination of the other groups. This is not found persuasive because the technical feature (an mRNA for use in synthesis of a protein comprising phosphorothioate groups) is not a special technical feature as it does not make a contribution over the prior art in view of Tohda et al. (1994, cited on IDS).
Tohda et al. teach the synthesis of dihydrofolate reductase (DHFR) in a cell free E. coli translation system, said system comprising the utilization of DHFR mRNA that comprises phosphorothioate groups (thio-mRNA) and which is synthesized by in vitro transcription of the DFHR gene in the presence of Sp diasteromers of ribonucleoside 5’-O-(1-thiotriphophates) (See Abstract and Materials and Methods).
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a PCT national stage application of PCT/JP2020/037706, filed 10/05/2020, is acknowledged and claims foreign priority to JP2019-188411.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/10/2022 and 08/29/2023 were filed prior to the mailing of the instant first Office action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. A copy of Form PTO/SB/08 is attached to the instant Office action.
Drawings
The presented drawings (Figures 1-10) have been considered by the examiner
Nucleotide and/or Amino Acid Sequence Disclosures
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that Figure 7 depicts sequences without its respective SEQ ID NO either in the figure itself or in the figure description. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The term “nt” in claims 1 (line 8), is a relative term which renders the claim indefinite. The term “nt” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Examiner requests the term "nt" be changed to "nucleotide".
Claim Rejections - 35 USC § 102
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.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ueda, et. al., Phosphorothioate-containing RNAs show mRNA activity in the prokaryotic translation systems in vitro, Nucleic Acids Research, Vol 19, No 3, pages 547-552, 1991 (applicant’s IDS, page 2, No. 9, 11/10/2022) and as evidenced by Robinson, et. al., Biology, Genetic Code, pages 129-130, 2002 and Robinson, et.al., Biology, Protein Synthesis, page 14, 2002.
Claim 1 is drawn to an mRNA for use in synthesis of a protein comprising: a translation region containing a start codon and a stop codon; and an untranslated region positioned on the 5'-end side of the start codon, some of phosphate groups within the range of at least from the 5' end of the untranslated region to 15 nucleotides on the 3'- end side of the start codon being substituted with phosphorothioate groups. Regarding Claim 1, Ueda anticipates utilizing an mRNA transcript for use in the synthesis of a protein (page 548, first paragraph). The mRNA transcript synthesized by Ueda is made by in vitro transcription and incorporation of labeled phosphorothioate nucleotide triphosphates is accomplished when they are added into the transcription reaction mixture, thus labeling the corresponding phosphate groups of the mRNA backbone including some of the phosphate groups within range of at least the 5’ end of the untranslated region to 15 nucleotides on the 3’ end side of the start codon. Robinson et. al. evidences that a start and stop codon are required for protein translation to occur from the translation region (page 14, Initiation section; page 17-18, Termination section) and evidencing an untranslated region positioned on the 5’-end side of the start codon (page 14, Initiation in Prokaryotes section).
Claim 2 is drawn to an mRNA wherein at least some of the phosphate groups at two or more positions are the phosphorothioate groups. Regarding claim 2, Ueda anticipates this by utilizing phosphorothioate labeled nucleotide triphosphates in their synthesis of mRNA (page 548, first paragraph).
Claim 3 is drawn to an mRNA wherein at least some of the phosphate groups in the untranslated region and at least some of the phosphate groups in the translation region are the phosphorothioate groups. Regarding claim 3, Ueda anticipates this through utilization of phosphorothioate labeled nucleoside triphosphates in their generation of mRNA transcripts (page 548, first paragraph). mRNA transcripts utilized for protein synthesis will have a translated and an untranslated region, where according to the labeling method of Ueda, at least some of the phosphate groups in those regions will contain the phosphorothioate groups..
Claim 4 is drawn to an mRNA wherein two or more kinds of nucleotides of adenosine monophosphate, guanosine monophosphate, cytidine monophosphate, and uridine monophosphate, which form an mRNA, are phosphorothioate groups. Regarding claim 4, Udea anticipates this through utilization of phosphorothioate labeled nucleotide triphosphates to generate labeled mRNA transcripts where two or more kinds of nucleotides are phosphorothioate groups (page 548, first paragraph).
Claim 5 is drawn to an mRNA wherein the untranslated region contains a Shine-Dalgarno sequence. By utilizing the method of Ueda, one could label the untranslated region of the synthesized mRNA containing a Shine-Dalgarno sequence with phosphorothioate groups (page 548, first paragraph). Regarding claim 5, Robinson evidences that the untranslated region contains a Shine-Dalgarno sequence necessary to prime the correct place to start translating a protein. These untranslated regions, containing a Shine-Dalgarno sequence in mRNA, are a requirement for proper ribosome assembly for protein translation to occur.
Claim 6 is drawn to an mRNA wherein phosphate groups at ten or more positions within the range of at least from the 5' end of the untranslated region to 15 nucleotides on the 3'-end side of the start codon are substituted with phosphorothioate groups, and the phosphorothioate group is contained in both of the Shine-Dalgarno sequence and the translation region. Regarding claim 6, Ueda’s mRNA synthesis method (page 548, first paragraph) anticipates this through the utilization of phosphorothioate labeled nucleoside triphosphates to generate mRNA transcripts to be utilized for translation into protein. It is known in the art that in order for protein translation to occur, mRNA transcripts require an untranslated region (containing a Shine-Dalgarno sequence) and a translation region utilized for coding protein evidenced by Robinson (page 14, Initiation in Prokaryotes section).
Status of the Claims
Claims 1-6 are rejected.
Conclusion
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/A.S./Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656