Prosecution Insights
Last updated: April 19, 2026
Application No. 18/277,438

PROTEIN TRANSLATION SYSTEM

Non-Final OA §103
Filed
Aug 16, 2023
Examiner
FRONDA, CHRISTIAN L
Art Unit
1652
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Tsinghua University
OA Round
1 (Non-Final)
82%
Grant Probability
Favorable
1-2
OA Rounds
2y 8m
To Grant
96%
With Interview

Examiner Intelligence

Grants 82% — above average
82%
Career Allow Rate
1099 granted / 1333 resolved
+22.4% vs TC avg
Moderate +14% lift
Without
With
+14.1%
Interview Lift
resolved cases with interview
Typical timeline
2y 8m
Avg Prosecution
44 currently pending
Career history
1377
Total Applications
across all art units

Statute-Specific Performance

§101
4.5%
-35.5% vs TC avg
§103
26.2%
-13.8% vs TC avg
§102
7.2%
-32.8% vs TC avg
§112
37.1%
-2.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1333 resolved cases

Office Action

§103
DETAILED ACTION The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1, 2, 5-7, 9, 10, 12, 14, 15, 17, 19, 21-23, 26-28, and 30 are pending in the instant application. Applicant's election with traverse of Invention 1 in the reply filed on 11/17/2025 is acknowledged. The arguments have been considered but are not persuasive. The combination of the references teachings of WO2019193416 (2019-10-10; IDS filed 08/07/2025) in view of WO2016154675 (2016-10-06; IDS filed 10/26/2023), Kanda et al. (Biochemical and Biophysical Research Communications, 270(3): 1136-1139, 21 April 2000; IDS filed 10/26/2023), Wang et al.(Chem Volume 5, Issue 4, 11 April 2019, Pages 848-857; PTO 892) render obvious Invention 1 as stated below in the rejection of claims 1, 2, 5-7, 9, 10, 12 under 35 U.S.C. 103. Thus, the same or corresponding technical feature was known in the prior art and therefore cannot make a contribution over the prior art. Since the inventions lack the same or corresponding special technical feature, then Inventions 1-5 are not so linked as to form a single general inventive concept under PCT Rule 13.1. Claims 14, 15, 17, 19, 21-23, 26-28, 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL. Claims 1, 2, 5-7, 9, 10, 12 are under consideration in this Office Action. 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 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. Claims 1, 2, 5-7, 9, 10, 12 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019193416 (2019-10-10; IDS filed 08/07/2025) in view of WO2016154675 (2016-10-06; IDS filed 10/26/2023), Kanda et al. (Biochemical and Biophysical Research Communications, 270(3): 1136-1139, 21 April 2000; IDS filed 10/26/2023), Wang et al.(Chem Volume 5, Issue 4, 11 April 2019, Pages 848-857; PTO 892). WO2019193416 teaches in vitro translation systems where cell-free translation reactions were performed following previously developed but slightly modified protocol, which includes in the reaction a lysate (cell-free translation mix, like E. coli S30 cell extract) and 10 mM Mg(OAc)2, and other components (page 57, lines 20-30; claims 16-18). WO2019193416 teaches the in vitro translation requires tRNAs, which can carry an unnatural amino acid, like D-amino acids (claim 61, page 35, lines 1-2), and an mRNA (see Examples 1-5). WO2019193416 teaches that the in vitro method for producing the polypeptides, does not need the presence of the aminoacyl tRNA synthetase (see for a example claim 16) and Flexizymes can be used to mediate the aminoacylation (page 41, line 12). WO2019193416 teach that the tRNAs were added at concentrations of about 20 μM in the translation reaction (legend to Figs. 2, 6, 8), thus, there is at least a concentration for all tRNAs of about 400 μM concentration; and the proteins produced include enzymes (see last paragraphs of the Introduction and the Discussion). The teachings of the reference differ from the claims in that the reference does not teach that the tRNA comprises L-ribonucleic acid residues (L-tRNA) WO2016154675 teaches a cell-free translation system comprising tRNAs and an mRNA, using a Flexizyme that can charge non-natural amino acids onto tRNAs in vitro (see claims, Fig. 28, examples) where D-amino acids are included (page 17, lines 2-3). WO2016154675 teaches that the system comprises a cell-free S30 lysate and for the cell-free translation reactions, the system uses a standard protocol with optimized magnesium acetate (Mg(Ac)2) at 10 mM final concentration (p.25, lines 1-4). WO2016154675 teaches that the the tRNA preparations were precipitated by ethanol and then dissolved in water, thus, no magnesium is added with the tRNAs (pages 57-58); and the tRNA mixtures were at 1 μg/μI final concentration. Kanda et al. teach in vitro translation systems using mRNA, tRNAs, a cell-free translation mix (E. coli S30 cell extract, which is depleted from tRNA) and the concentration of Mg2+ is as high as 14 Mm and with 10 mM the translation efficiency was highest (See Examples 1-3, Fig. 3, 6). Kanda et al. teach that the system uses a cell-free crude cell extract S30 from E. coli. for the in vitro translation (abstract). Kanda et al. teach that in the cell-free protein synthesis, the initial concentration of each unnatural aminoacyl-tRNA was 4 μM (p. 1137, col. 2, para. 2), and in some cases unnatural amino acids are incorporated. Wang et al. teach chemical synthesis and use of a 76-nt L-tRNA (mirror image tRNA) in mirror-image transcription experiments; where synthetic mutants of the DNA polymerase Dpo4 were used to transcribe L-tRNA from L-DNA templates and the L-tRNA was charged with D-amino acids. See entire publication and abstract especially Results section, Experimental Procedures section, Discussion section, and pages 849-856 Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by combining the components of the translation systems of WO2016154675 and Kanda et al. into the translation system WO2019193416 with the L-tRNA charged with D-amino acids taught by Wang et al. wherein a concentration of Mg2+ in the system is less than 100 mM. It would have been obvious to adjust the concentration of Mg2+ in the system, using any unnatural amino acid residue including any D-amino acid residue, preparing the L-tRNA using D-polymerase as routine optimization and/or as desired. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a simple system for producing a protein using the L-tRNA charged with D-amino acids. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because preparing and making translation systems for producing a protein are known in the art as shown by reference teachings. Hence, the claimed invention as a whole is prima facie obvious. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272 0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM-5:00PM. 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, Robert Mondesi can be reached on (408)918-7584. 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. /CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
Read full office action

Prosecution Timeline

Aug 16, 2023
Application Filed
Mar 07, 2026
Non-Final Rejection — §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
82%
Grant Probability
96%
With Interview (+14.1%)
2y 8m
Median Time to Grant
Low
PTA Risk
Based on 1333 resolved cases by this examiner. Grant probability derived from career allow rate.

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