Prosecution Insights
Last updated: July 17, 2026
Application No. 17/777,770

Modification of tRNA T-Stem for Enhancing N-Methyl Amino Acid Incorporation

Non-Final OA §102§103§112§DP
Filed
May 18, 2022
Priority
Nov 19, 2019 — JP 2019-209114 +1 more
Examiner
KONOPKA, CATHERINE ANNE
Art Unit
1632
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The University of Tokyo
OA Round
1 (Non-Final)
59%
Grant Probability
Moderate
1-2
OA Rounds
0m
Est. Remaining
99%
With Interview

Examiner Intelligence

Grants 59% of resolved cases
59%
Career Allowance Rate
112 granted / 191 resolved
-1.4% vs TC avg
Strong +65% interview lift
Without
With
+65.0%
Interview Lift
resolved cases with interview
Typical timeline
3y 10m
Avg Prosecution
67 currently pending
Career history
247
Total Applications
across all art units

Statute-Specific Performance

§101
1.4%
-38.6% vs TC avg
§103
45.6%
+5.6% vs TC avg
§102
4.1%
-35.9% vs TC avg
§112
10.9%
-29.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 191 resolved cases

Office Action

§102 §103 §112 §DP
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 . Application Status The preliminary amendment filed May 18, 2022 is acknowledged. Claims 1-16 are pending and under examination. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency #1 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Specifically, the sequences appearing in the tables are not identified. It is noted that on page 59 of the Specification some of the sequences in the tables are identified. However, this is not sufficient. Each sequence should have its corresponding SEQ ID NO listed next to the sequence. For the tables, adding a column to include the SEQ ID NO is sufficient. Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Specific deficiency #2 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Required response – Applicant must provide: Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers; AND/OR A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Specific deficiency #3 - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825. Claims 7 and 13 and pages 5 and 19 of the Specification recite AGGGG(N4)mCCCCU (SEQ ID NO 1). However, SEQ ID NO 1 is AGGGGNCCCCU. “(N4)m” is recited as four Ns (i.e., undisclosed nucleotides) that can occur M times. Such sequences as AGGGGNNNNCCCCU (m=1) or AGGGGNNNNNNNNCCCCU (m=2) are not present in the sequence listing. Required response – Applicant must provide: A "Sequence Listing" part of the disclosure, as described above in item 1); as well as An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2); A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4). If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter; If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide: A replacement CRF in accordance with 1.825(b)(6); and Statement according to item 2) a) or b) above. Claim Objections Claims 1, 5-6, and 11-12 objected to because of the following informalities: Claims 1, 5-6 and 11-12 recites “a T-stem in which N1N2GGN3 and N4CCN5U form a pair…” The appropriate terminology for nucleotides that “form a pair” is “hybridize”. As such, it is recommended that the claims use “hybridize” instead of “form a pair” to described the relationship between the bases in the T-stem. See suggested claim language below. Claim Interpretation Claim 1 recites “A tRNA having a T-stem… and encoding an N-methyl amino acid…” A tRNA does not inherently contain an amino acid. A tRNA can be classified as “charged” meaning that an amino acid has been conjugated to the 3’ end, or “uncharged” meaning that no amino acid is attached to its 3’ end. “Encoding an N-methyl amino acid” is interpreted as functional language. As indicated in the §102 rejection below, any tRNA can function to encode an N-methyl amino acid because amino acids that are attached to a tRNA can be N-methylated chemically in vitro. Therefore, claim 1 broadly, but reasonably encompasses an uncharged tRNA having the recited sequence in the T-stem. If Applicant desires to include the N-methyl amino acid as a required feature, the following claim language is suggested: “A charged tRNA comprising (1) a T-stem comprising N1N2GGN3 and N4CCN5U that hybridize; wherein N1 is G or A, one of N2 and N5 is G and the other one is C, and N3 and N4 are any nucleotides that can hybridize; and (2) an N-methyl amnio acid.” Claim Rejections - 35 USC § 112(d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claims 9-10 and 15-16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 9-10 and 15-16 recite a “peptide library produced by the method of claim 3 [claim 4]”. Thus claims 9-10 and 15-16 encompass peptides that are produced using a translation system in which the N-methyl amino acid is removed from the tRNA and integrated into a growing peptide chain. As such, the peptide library does not necessarily include the tRNA itself. 35 CFR 1.75 states “One or more claims may be presented in dependent form, referring back to and further limiting another claim or claims in the same application.” Because claims 9-10 and 15-16 refer back to claims 3 or 4, which in turn refer back to claim 1, claims 9-10 and 15-16 are dependent claims of claim 1. Since claims 9-10 and 15-16 do not require the tRNA of claim 1, the claims fail to include all the limitations of claim 1, from which they depend. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 112(b) 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. Claims 1-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 1 recites N1 is G or A; one of N2 and N5 is G and the other one is C, and N3 and N4 are any amino acids forming a pair.” Amino acids are not known in the art to be included in tRNAs and it is not clear what amino acids can form a pair. As such, claim 1 is confusing and the structure of the tRNA is indefinite. Claims 2-16 are rejected for depending from claim 1 and not remedying the indefiniteness. Claims 5 and 11 recite “a step of preparing…., wherein in the preparation step, which tRNA is charged, a tRNA having a T-stem in which N1N2GGN3 and N4CCN5U form a pair or a tRNA other than the tRNA having a T-stem in which N1N2GGN3 and N4CCN5U form a pair is determined prior to charging with an N-methyl amino acid”. It is not clear what step is being performed or what is being “determined” in this step. It is possible that the determining step is choosing which tRNAs to use in the preparation. However, if tRNAs are used in which N1N2GGN3 and N4CCN5U don’t hybridize, then the claim would not require all the limitations of claim 1. Claims 6-7 and 12-13 also recite a determining step. Similar to claims 5 and 11 it is not clear what is being determined and how the determining step is limiting the claimed method. If claims 5-7 and 11-13 are meant to recite a charging step only in which the engineered tRNAs are charged with N-methyl amino acids and non-engineered tRNA are charged with natural amino acids, the following claim language is suggested: “The method according to claim 3 [claim 4], further comprising (1) charging the tRNA having the modified T-stem with an N-methyl amino acid, and (2) charging tRNAs having an unmodified T-stem with non-N-methyl amino acids”. If the claim language is adopted, it is further suggested that claim 1 recite: “A charged tRNA comprising (1) a modified T-stem comprising N1N2GGN3 and N4CCN5U that hybridize…” Claims 7 and 13 recite AGGGG(N4)mCCCCU. “(N4)m” is interpreted as four Ns (i.e., four undisclosed nucleotides) that can occur M times. However, the claim does not define “m”. As such it is not clear how many sets of 4 N’s the sequence can have, rendering the structure of the tRNA and the claim indefinite. Claim Rejections - 35 USC § 102 - Katoh 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 1-4, 9 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Katoh (Katoh et al., Nucleic Acids Research (2017) 45: 12601-12610) and evidenced by Kawakami (Kawakami et al., Chemistry and Biology (2008), 15: 32-42). As indicated above in paragraph 5, the tRNA in claim 1 is interpreted as encompassing both charged and uncharged versions of the tRNA. Unless claims recite charging a tRNA with an N-methyl amino acid or require the production of a peptide comprising N-methyl amino acids using the claimed tRNA, the claims are interpreted as only requiring the tRNA with the recited sequence in the T-stem. Regarding claim 1, Katoh teaches a tRNA comprising a T-Stem having the sequence 5’- AGGGG---CCCCU in the T-stem (i.e., a tRNA having N1N2GGN3 and N4CCN5U that hybridize; wherein N1 is G or A, one of N2 and N5 is G and the other one is C, and N3 and N4 are any nucleotides that can hybridize) (Fig 4). Katoh teaches the engineered tRNA can be charged with activated D- and L- amino acids using Flexizymes (page 12602, ¶4-5). Katoh is silent regarding whether the tRNAs with the modified T-stems can be charged with N-methyl amino acids. Kawakami teaches that any tRNA can be charged with an N-methyl amino acid using a flexizyme (Figure 1). Therefore, the tRNA with the modified T-stem disclosed in Katoh is capable of “encoding an N-methyl amino acid”. Regarding claim 2, Katoh teaches a translation system comprising the tRNA with the modified T-stem and Ef-Tu (Fig 1, ¶ spanning pages 12602-12603). Regarding claims 3-4, 9 and 15, the claims do not recite the peptide library having N-methyl amino acids; therefore the “encoding N-methyl amino acid” from claim 1 is still interpreted as merely functional language of the tRNA. Katoh teaches producing two peptides from two mRNAs (i.e., a peptide library and a peptide-mRNA complex library) using Pro1E2 (Fig 6), which uses a tRNA having the modified T-stem sequence (Fig 4). Claim Rejections - 35 USC § 102 - Subtelny Claims 9-10 and 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Subtelny (Subtelney et al., JACS (2008), 130: 6131-6136). Claims 9 and 15 recite “a peptide [peptide-mRNA complex] library produced by the method of claim 3 [claim 4]). Thus, claims 9-10 and 15-16 are product by process claims. The claims do not require the steps of the methods. Rather this product-by-process will be examined according to the structure of the libraries that are produced by the methods of claims 3 and 4. See. MPEP 2113. The specification indicates that the methods produce a library of peptides that have one or more methylated amino acids and can include the mRNA (see e.g., Figs 2 and 4). Therefore, claims 9-10 encompass at least two peptides (i.e., a library) wherein at least one (claims 9 and 15) or two (claims 10 and 16) amino acids in each peptide is methylated. Claims 15-16 encompass at least two peptides and a mRNA (i.e., a library). Regarding claims 9-10, Subtelny teaches an in vitro translation system that produced peptides with two and three methylated amino acids (Fig 4). Regarding claims 15-16, Subtelny teaches the peptide library was produced by in vitro translation was initiated by providing mRNA to ribosomes and tRNAs charged with N-methyl amino acids (page 6133, ¶3-4). Therefore, during the process of the peptide library there existed an N-methyl peptides in association (i.e., a complex) with mRNA. Claim Rejections - 35 USC § 103 – Katoh and Kawakami 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 5-8, 10-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Katoh (Katoh et al., Nucleic Acids Research (2017) 45: 12601-12610) and evidenced by Kawakami (Kawakami et al., Chemistry and Biology (2008), 15: 32-42). The teachings of Katoh and Kawakami are recited above for claims 1-4, 9 and 15 and are incorporated here. Briefly, Katoh teaches a tRNA comprising the sequence 5’- AGGGG---CCCCU in the T-stem (i.e., a tRNA having N1N2GGN3 and N4CCN5U that hybridize; wherein N1 is G or A, one of N2 and N5 is G and the other one is C, and N3 and N4 are any nucleotides that can hybridize) (Fig 4). Katoh teaches the engineered tRNA can be charged with activated D- and L- amino acids using Flexizymes (page 12602, ¶4-5). Kawakami teaches that Flexizymes can also be used to charge tRNA with N-methyl amino acids (Figure 1). Although Katoh, as evidenced Kawakami, teaches a tRNA comprising the claimed T-stem sequence that can be charged with N-methyl amino acids, Kawakami does not demonstrate the tRNA actually charged with N-methyl amino acids or using the meAA-tRNA to produce N-methylated peptides. However, Katoh also suggests evaluating whether the engineered tRNA could be used to produced N-methylated peptides (page 12609, ¶2). Regarding claims 5-7, 10-13 and 16, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have charged Katoh’s engineered tRNA comprising the claims T-stem sequence with an N-methyl amino acid and used in a method to produce an N-methylated peptide and peptide-mRNA library. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that Katoh’s tRNA could be charged with N-methyl amino acids for the purpose of creating the peptide library because Kawakami teaches that the flexizymes used by Katoh to charge the tRNA with different amino acids can also be used to charge tRNAs with N-methyl amino acids. The skilled artisan would have been motivated to have used Katoh’s tRNA to produce a peptide and peptide-mRNA library with N-methylated amino acids because Katoh suggests it. Regarding claims 8 and 14, Katoh teaches the tRNA with the claimed T-stem sequence improves the affinity between the charged tRNA and Ef-Tu (Figure 1). Katoh teaches the affinity between charged tRNAs and EF-Tu depends on the specific combination of amino acid and tRNA anti-codon sequence (page 12605, ¶7). Katoh teaches delta G values for several tRNA and amino acid combinations as -8.8, -9.3 and -11.7 kcal/mol (page 12605, ¶7). Katoh teaches previous reports of engineering the T-stem with the claimed sequence improved the affinity (i.e., lowered the delta G) with EF-Tu (page 12605, ¶7). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have chosen N-methylated tRNAs that have a delta G between -7.5 and -10 kcal/mol because the claimed affinities are in the known range that promote in vitro translation as indicated by Katoh. It would have been entirely predictable that the engineered tRNA charged with N-methyl amino acids would have the claimed affinities because N-methylation is predicted to lower the EF-Tu affinity, but Katoh teaches the engineered T-stem sequence increases the affinity to counteract the reduced affinity. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim of U.S. Patent No. 11946042 in view of Katoh (Katoh et al., Nucleic Acids Research (2017) 45: 12601-12610) and evidenced by Kawakami (Kawakami et al., Chemistry and Biology (2008), 15: 32-42). Patented claim 1 recites A tRNA comprising the base sequence of SEQ ID NO: 1 and encoding a non-proteinogenic amino acid, wherein said tRNA is an elongator tRNA whereby the base at its 5′ end forms a base pair with corresponding base on the 3′ side of its acceptor stem. Patented claim further comprising AGGGG(N14)mCCCCU wherein N14 represents an arbitrary base, m stands for an integer of 1 or more, (N14)m form a T-loop, and AGGGG forms a base pair with UCCCC (i.e., the same sequence recited in examined claims 1, 5-7, 11-13). Patented claim 11 recited A translation system for the synthesis of a peptide having two or more consecutive non-proteinogenic amino acids, comprising the tRNA of claim 1. Patented claims 12 recites A method of constructing a peptide library, comprising a step of translating in a cell-free translation system by using the tRNA of claim 1. Patented claim A method of constructing a library of a complex between a peptide and an mRNA encoding the peptide, comprising a step of translating in a cell-free translation system by using the tRNA of claim 1. The patented claims do not recite the non-proteinogenic amino acid attached to the tRNA is an N-methyl amino acid or specifically making a peptide library comprising N-methylated amino acids. The teachings of Katoh and Kawakami are recited above in paragraphs 22-24 and 32-34 an incorporated here. The obviousness of using the patented tRNA with the engineered T-stem to attach an N-methylated amino acid and used in methods combined with mRNAs and EF-Tu to make peptide libraries with N-methylated amino acids is recited above in paragraph 35 and 36. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE KONOPKA whose telephone number is (571)272-0330. The examiner can normally be reached Mon - Fri 7- 4. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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Prosecution Timeline

May 18, 2022
Application Filed
Jun 03, 2026
Non-Final Rejection mailed — §102, §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
59%
Grant Probability
99%
With Interview (+65.0%)
3y 10m (~0m remaining)
Median Time to Grant
Low
PTA Risk
Based on 191 resolved cases by this examiner. Grant probability derived from career allowance rate.

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