Granted Patent
B2
US 12,258,369 · App. 18/467,224 · Granted Mar 25, 2025
Compositions and methods for synthesizing 5′-capped RNAs
Inventors:
Richard I. Hogrefe (San Diego, CA); Alexandre Lebedev (San Diego, CA); Anton P. McCaffrey (San Diego, CA); Dongwon Shin (San Diego, CA)
Assignee:
TriLink BioTechnologies, LLC
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Abstract
Provided herein are methods and compositions for synthesizing 5′Capped RNAs wherein the initiating capped oligonucleotide primers have the general form m7 Gppp[N 2′Ome ] n [N] m wherein m7 G is N7-methylated guanosine or any guanosine analog, N is any natural, modified or unnatural nucleoside, “n” can be any integer from 0 to 4 and “m” can be an integer from 1 to 9.
Claims (50)
1. An initiating capped oligonucleotide primer comprising the following structure:
wherein:
each of B 1 through Bio is independently a natural, modified or unnatural nucleoside base;
M is 0 or 1;
L is 0 or 1;
q 1 is 1 and each of q 2 through q 9 is independently 0 or 1;
each R 1 is independently H or methyl;
R 2 and R 3 are independently H, OH, alkyl, O-alkyl, halogen, a linker or a detectable marker;
each of X 1 through X 13 is independently O or S;
each of Y 1 through Y 13 is independently OH, SH, BH 3 , aryl, alkyl, O-alkyl or O-aryl;
each of Z 0 through Z 22 is independently O, S, NH, CH 2 , C(halogen) 2 or CH (halogen); and
each of R 4 through R 12 is independently H, OH, O-methyl, or a detectable marker, wherein:
B 1 is complementary to a nucleoside base on a nucleic acid template at transcription template position +1 from the transcription start site,
B 2 through B 9 , if present, are complementary to the respective nucleoside bases on the nucleic acid template at transcription template position +2 and so on from the transcription start site, and
B 10 , the last nucleoside base of initiating capped oligonucleotide primer, is complementary to the last hybridized transcription template nucleotide.
2. The initiating capped oligonucleotide primer of claim 1 , wherein each Ris H.
3. The initiating capped oligonucleotide primer of claim 1 , wherein R 2 and R 3 are each independently OH or O-methyl.
4. The initiating capped oligonucleotide primer of claim 1 , wherein R 4 is OH or O-methyl.
5. The initiating capped oligonucleotide primer of claim 1 , wherein each of B 1 through B 10 is independently adenine, N 6 -methyladenine, guanine, cytosine, or uracil.
6. The initiating capped oligonucleotide primer of claim 1 , wherein B 1 is adenine or N 6 -methyladenine.
7. The initiating capped oligonucleotide primer of claim 1 , wherein B 1 is guanine.
8. The initiating capped oligonucleotide primer of claim 1 , wherein B 10 is guanine.
9. The initiating capped oligonucleotide primer of claim 1 , wherein B 10 is uracil.
10. The initiating capped oligonucleotide primer of claim 1 , wherein each of q2 through q 9 is 0.
11. The initiating capped oligonucleotide primer of claim 10 , wherein B 1 is adenine, N 6 -methyladenine, or guanine.
12. The initiating capped oligonucleotide primer of claim 10 , wherein B 10 is guanine or uracil.
13. The initiating capped oligonucleotide primer of claim 10 , wherein B 1 dis adenine and B 10 is guanine.
14. The initiating capped oligonucleotide primer of claim 10 , wherein B 1 is N 6 -methyladenine and B 10 is guanine.
15. The initiating capped oligonucleotide primer of claim 10 , wherein B 1 is adenine and B 10 is uracil.
16. The initiating capped oligonucleotide primer of claim 10 , wherein B 1 is guanine and B 10 is guanine.
17. The initiating capped oligonucleotide primer of claim 10 , wherein B 1 is cytosine and B 10 is guanine.
18. The initiating capped oligonucleotide primer of claim 10 , wherein R 1 is H and R 4 is O-methyl.
19. The initiating capped oligonucleotide primer of claim 1 , wherein the initiating capped oligonucleotide primer has the following structure:
20. The initiating capped oligonucleotide primer of claim 1 , wherein the initiating capped oligonucleotide primer has the following structure:
21. The initiating capped oligonucleotide primer of claim 1 , wherein the initiating capped oligonucleotide primer has the following structure:
22. The initiating capped oligonucleotide primer of claim 1 , wherein the initiating capped oligonucleotide primer has the following structure:
23. The initiating capped oligonucleotide primer of claim 1 , wherein q 1 is 1, q 2 is 1, and each of q 3 through q 9 is 0.
24. The initiating capped oligonucleotide primer of claim 23 , wherein B 1 is adenine, B 2 is guanine, and Bio is guanine.
25. The initiating capped oligonucleotide primer of claim 1 , wherein the initiating capped oligonucleotide primer has the following structure:
26. An RNA molecule comprising the initiating capped oligonucleotide primer according to claim 1 .
27. An isolated cell containing an RNA molecule comprising the initiating capped oligonucleotide primer according to claim 1 .
28. A pharmaceutical composition comprising an RNA molecule comprising the initiating capped oligonucleotide primer according to claim 1 and a pharmaceutical acceptable carrier.
29. A complex comprising an initiating capped oligonucleotide primer and a DNA template,
wherein the initiating capped oligonucleotide primer comprises a structure:
wherein
B 1 is guanine;
B 2 and B 3 are independently a natural, a modified, or an unnatural nucleoside base; and
R 1 , R 2 , R 3 and R 4 are independently OH or O-methyl;
wherein the DNA template comprises a promoter region comprising a transcriptional start site having a first nucleotide at nucleotide position +1, a second nucleotide at nucleotide position +2, and a third nucleotide at nucleotide position +3; and
wherein the initiating capped oligonucleotide primer is hybridized to the DNA template at least at nucleotide positions +1, +2, and +3.
Assignments (3)
SECURITY INTEREST
Recorded Jun 3, 2026
From: TRILINK BIOTECHNOLOGIES, LLC; CYGNUS TECHNOLOGIES, LLC; GLEN RESEARCH, LLC
To: BSP AGENCY, LLC, AS COLLATERAL AGENT
Reel/Frame 074835/0788 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 31, 2024
From: HOGREFE, RICHARD I.; LEBEDEV, ALEXANDRE; MCCAFFREY, ANTON P.; SHIN, DONGWON
To: TRILINK BIOTECHNOLOGIES, INC.
Reel/Frame 066309/0913 →
CHANGE OF NAME
Recorded Jan 31, 2024
From: TRILINK BIOTECHNOLOGIES, INC.
To: TRILINK BIOTECHNOLOGIES, LLC
Reel/Frame 066384/0739 →
Continuity (4)
Continuation
15761957
Provisional Application
62221248
· Sep 21, 2015
References Cited (400)
US 5837852A
· Chung et al.
· 1998
[cited by applicant]
US 6762298B2
· Beaucage et al.
· 2004
[cited by applicant]
US 7074596B2
· Darzynkiewicz et al.
· 2006
[cited by applicant]
US 8153773B2
· Jemielity et al.
· 2012
[cited by applicant]
US 8344118B2
· Kore et al.
· 2013
[cited by applicant]
US 8557972B2
· Reh et al.
· 2013
[cited by applicant]
US 20030194759A1
· Darzynkiewiz et al.
· 2003
[cited by applicant]
US 20060293240A1
· Ron
· 2006
[cited by examiner]
US 20070281308A1
· Zon et al.
· 2007
[cited by applicant]
US 20080248469A1
· Spier
· 2008
[cited by applicant]
US 20100233757A1
· Jemielity et al.
· 2010
[cited by applicant]
US 20100261231A1
· Kore et al.
· 2010
[cited by applicant]
US 20100304389A1
· Kore et al.
· 2010
[cited by applicant]
US 20120045461A1
· Hartmann et al.
· 2012
[cited by applicant]
US 20120156751A1
· Kore et al.
· 2012
[cited by applicant]
US 20130115272A1
· de Fougerolles et al.
· 2013
[cited by applicant]
AU 2013243953A1
· 2014
[cited by examiner]
CA 2692906A1
· 2008
[cited by applicant]
CA 2850624A1
· 2013
[cited by applicant]
CA 2903488A1
· 2014
[cited by applicant]
CN 101855231A
· 2010
[cited by applicant]
CN 103974724A
· 2014
[cited by applicant]
CN 104072561A
· 2014
[cited by applicant]
CN 107501370A
· 2017
[cited by applicant]
CN 110511939A
· 2019
[cited by applicant]
EP 0081099A2
· 1983
[cited by applicant]
EP 2167523A2
· 2010
[cited by applicant]
EP 2763701A1
· 2014
[cited by applicant]
EP 2971098A1
· 2016
[cited by applicant]
EP 3492109A1
· 2019
[cited by applicant]
EP 3495505A1
· 2019
[cited by applicant]
EP 3682905A1
· 2020
[cited by applicant]
EP 3352584B1
· 2021
[cited by applicant]
EP 4015005A1
· 2022
[cited by applicant]
JP 2009544754A
· 2009
[cited by applicant]
JP 2014530601A
· 2014
[cited by applicant]
JP 2016515216A
· 2016
[cited by applicant]
JP 2017113029A
· 2017
[cited by applicant]
JP 2018527015A
· 2018
[cited by applicant]
JP 2018166528A
· 2018
[cited by applicant]
JP 2019208511A
· 2019
[cited by applicant]
JP 6909157B2
· 2021
[cited by applicant]
JP 2022060269A
· 2022
[cited by applicant]
KR 20140068245A
· 2014
[cited by applicant]
KR 20190099538A
· 2019
[cited by applicant]
KR 102366490B1
· 2022
[cited by applicant]
MX 354267B
· 2018
[cited by applicant]
WO 2008016473A2
· 2008
[cited by applicant]
WO 2008157688A2
· 2008
[cited by applicant]
WO 2009058911A2
· 2009
[cited by applicant]
WO 2010071587A1
· 2010
[cited by applicant]
WO 2011157617A1
· 2011
[cited by applicant]
WO 2013052523A1
· 2013
[cited by applicant]
WO 2014152673A1
· 2014
[cited by applicant]
WO 2016098028A1
· 2016
[cited by applicant]
WO 2017053297A1
· 2017
[cited by applicant]
WO 2017066797A1
· 2017
[cited by applicant]
WO 2019175356A1
· 2019
[cited by applicant]
WO 2021162566A1
· 2021
[cited by applicant]
WO 2021162567A1
· 2021
[cited by applicant]
WO 2021214204A1
· 2021
[cited by applicant]
WO 2022006368A2
· 2022
[cited by applicant]
U.S. Appl. No. 18/408,431, filed 2024.
[cited by examiner]
Chinese Application No. CN202110537080.4 , “Office Action”, Jan. 13, 2024, 9 pages.
[cited by applicant]
Chinese Application No. CN202311200887.4 , “Third Party Opinion”, Jan. 24, 2024, 10 pages (5 pages of Original Document and 5 pages of English Translation).
[cited by applicant]
Chinese Application No. CN2022110465917 , “Third Party Opinion”, Jan. 4, 2024, 27 pages.
[cited by applicant]
Chinese Application No. CN202310734863.0 , “Notice of Decision to Grant”, Jan. 2, 2024, 8 pages.
[cited by applicant]
European Application No. EP22175377.5 , “Intention to Grant”, Nov. 24, 2023, 9 pages.
[cited by applicant]
European Application No. EP23192203.0 , “Extended European Search Report”, Dec. 19, 2023, 9 pages.
[cited by applicant]
Auxiliary Request 1 (Clean), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 1 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 10 (Clean), C423910EP IRM JEE, 1 page.
[cited by applicant]
Auxiliary Request 10 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 11 (Clean), C423910EP IRM JEE, 1 page.
[cited by applicant]
Auxiliary Request 11 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 12 (Clean), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 12 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 2 (Clean), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 2 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 3 (Clean), C423910EP IRM JEE, pp. 1-2.
[cited by applicant]
Auxiliary Request 3 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 4 (Clean), C423910EP IRM JEE, pp. 1-2.
[cited by applicant]
Auxiliary Request 4 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 5 (Clean), C423910EP IRM JEE, pp. 1-2.
[cited by applicant]
Auxiliary Request 5 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 6 (Clean), C423910EP IRM JEE, pp. 1-2.
[cited by applicant]
Auxiliary Request 6 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 7 (Clean), C423910EP IRM JEE, pp. 1-2.
[cited by applicant]
Auxiliary Request 7 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 8 (Clean), C423910EP IRM JEE, pp. 1-2.
[cited by applicant]
Auxiliary Request 8 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
Auxiliary Request 9 (Clean), C423910EP IRM JEE, 1 page.
[cited by applicant]
Auxiliary Request 9 (Tracked), C423910EP IRM JEE, pp. 1-3.
[cited by applicant]
M7(3′-O-methyl)-G(5′)ppp(5′)G (ARCA), Catalog : AM8045, Accessed from Internet on Jan. 13, 2011, pp. 1-2.
[cited by applicant]
PGEM®-4Z Vector, Technical Bulletin, May 2009, 8 pages.
[cited by applicant]
Simplifying Manufacturing of Alphavirus Self-Amplifying RNA Replicons with CleanCap* Co-Transcriptional Capping, TriLink Biotechnologies part of Maravai LifeSciences, 15 pages.
[cited by applicant]
Synthesis of Translation Enhanced Capped Transcripts, Ambion, mMESSAGE mMACHINE® T7 Ultra Kit, Feb. 2014, pp. 1-36.
[cited by applicant]
Transcription of Protein-Coding Genes and Formation of Functional mRNA, Chapter 4.2, Basic Molecular Genetic Mechanisms, pp. 120-126.
[cited by applicant]
U.S. Appl. No. 15/761,957, Final Office Action mailed on Aug. 7, 2020, 7 pages.
[cited by applicant]
U.S. Appl. No. 15/761,957, Non-Final Office Action mailed on Jan. 16, 2020, 8 pages.
[cited by applicant]
U.S. Appl. No. 15/761,957, Notice of Allowance mailed on Oct. 22, 2020, 7 pages.
[cited by applicant]
U.S. Appl. No. 15/788,742, Notice of Allowance and Fees Due mailed on Jul. 9, 2019, 7 pages.
[cited by applicant]
U.S. Appl. No. 16/232,435, Non-Final Office Action mailed on Jun. 19, 2019, 11 pages.
[cited by applicant]
U.S. Appl. No. 16/232,435, Notice of Allowance mailed on Sep. 6, 2019, 7 pages.
[cited by applicant]
U.S. Appl. No. 16/232,435, Restriction Requirement mailed on Mar. 14, 2019, 6 pages.
[cited by applicant]
U.S. Appl. No. 16/232,435, Notice of Allowance mailed on Dec. 26, 2018.
[cited by applicant]
U.S. Appl. No. 16/371,317, Notice of Allowance mailed on Sep. 13, 2019, 10 pages.
[cited by applicant]
U.S. Appl. No. 17/091,422, Non-Final Office Action mailed on Jun. 30, 2023, 13 pages.
[cited by applicant]
U.S. Appl. No. 17/091,422, Notice of Allowance mailed on Sep. 13, 2023, 5 pages.
[cited by applicant]
U.S. Appl. No. 17/091,422, Titled: Compositions and Methods for Synthesizing 5′-Capped RNAs filed Nov. 6, 2020, 98 pages.
[cited by applicant]
U.S. Appl. No. 17/392,170, Corrected Notice of Allowability mailed on Jul. 18, 2022, 4 pages.
[cited by applicant]
U.S. Appl. No. 17/392,170, Corrected Notice of Allowability mailed on Jun. 9, 2022, 4 pages.
[cited by applicant]
U.S. Appl. No. 17/392,170, Non-Final Office Action mailed on Dec. 3, 2021, 18 pages.
[cited by applicant]
U.S. Appl. No. 17/392,170, Notice of Allowance mailed on May 17, 2022, 5 pages.
[cited by applicant]
U.S. Appl. No. 17/392,170, Titled: Compositions and Methods for Synthesizing 5′-Capped RNAs filed Aug. 2, 2021, 99 pages.
[cited by applicant]
U.S. Appl. No. 17/804,192, Corrected Notice of Allowability mailed on Jan. 3, 2023, 2 pages.
[cited by applicant]
U.S. Appl. No. 17/804,192, Non-Final Office Action mailed on Aug. 17, 2022, 8 pages.
[cited by applicant]
U.S. Appl. No. 17/804,192, Notice of Allowance mailed on Dec. 21, 2022, 5 pages.
[cited by applicant]
U.S. Appl. No. 90/014,910, Order Granting Request for Ex Parte Reexamination mailed on Dec. 17, 2021, 13 pages.
[cited by applicant]
U.S. Appl. No. 90/014,910, Reexam-Non-Final Office Action mailed on Apr. 14, 2022, 21 pages.
[cited by applicant]
U.S. Appl. No. 90/014,910, Request for Ex Parte Reexamination mailed on Nov. 23, 2021, 41 pages.
[cited by applicant]
Alberts et al., How Cells Read the Genome: From DNA to Protein, Chapter—6, 5th Edition, Molecular Biology of the Cell, 2008, pp. 331-339.
[cited by applicant]
Alberts et al., The Adaptive Immune System, Molecular Biology of the Cell, Garland Science, 5th edition, Jul. 2008, pp. 1539-1600.
[cited by applicant]
Allawi et al., Mapping of RNA Accessible Sites by Extension of Random Oligonucleotide Libraries with Reverse Transcriptase, RNA, vol. 7, No. 2, Feb. 2001, pp. 314-327.
[cited by applicant]
Australian Application No. 2016328645, First Examination Report mailed on Jun. 5, 2020, 6 pages.
[cited by applicant]
Australian Application No. 2016328645, Notice of Acceptance mailed on Apr. 30, 2021, 3 pages.
[cited by applicant]
Australian Application No. 2016328645, Second Examination Report mailed on Nov. 27, 2020, 3 pages.
[cited by applicant]
Australian Application No. 2021206780, First Examination Report mailed on Sep. 23, 2022, 3 pages.
[cited by applicant]
Australian Application No. 2021206780, Notice of Acceptance mailed on Mar. 27, 2023, 3 pages.
[cited by applicant]
Ausubel et al., Current Protocols in Molecular Biology, vol. 1, 1994, 18 pages.
[cited by applicant]
Axelrod et al., Transcription from Bacteriophage T7 and SP6 RNA Polymerase Promoters in the Presence of 3′-Deoxyribonucleoside 5′-Triphosphate Chain Terminators, Biochemistry vol. 24, No. 21, 1985, pp. 5716-5723.
[cited by applicant]
Banerjee5′-Terminal Cap Structure in Eucaryotic Messenger Ribonucleic Acids, Microbiological Reviews, vol. 44, No. 2, Jun. 1980, pp. 175-205.
[cited by applicant]
Beckert et al., Synthesis of RNA by In Vitro Transcription, Chapter 3, H. Nielsen (ed.), RNA, Methods in Molecular Biology, vol. 703, 2011, pp. 29-41.
[cited by applicant]
Belanger et al., Characterization of hMTr1, a Human Cap1 2′-O-Ribose Methyltransferase, Journal of Biological Chemistry, vol. 285, No. 43, Oct. 22, 2010, pp. 33037-33044.
[cited by applicant]
Bost et al., Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles, ACS Nano, vol. 15, No. 9, 2021, pp. 13993-14021.
[cited by applicant]
Both et al., Methylation-Dependent Translation of Viral Messenger RNAs in Vitro, Proceedings of the National Academy of Sciences, vol. 72, No. 3, Mar. 1975, pp. 1189-1193.
[cited by applicant]
Bouloy et al., Both the 7-methyl and the 2′-o-methyl Groups in the Cap of mRNA Strongly Influence Its Ability to Act as Primer for Influenza Virus RNA Transcription, Proceedings of the National Academy of Sciences, vol.…
[cited by applicant]
Brieba et al., Role of T7 RNA Polymerase His784 in Start Site Selection and Initial Transcription, Biochemistry, vol. 41, May 2002, pp. 5144-5149.
[cited by applicant]
Canadian Application No. 2,999,274, Notice of Allowance mailed on Nov. 18, 2022, 1 page.
[cited by applicant]
Canadian Application No. 2,999,274, Office Action mailed on May 16, 2023, 3 pages.
[cited by applicant]
Canadian Application No. 2,999,274, Office Action mailed on May 25, 2022, 3 pages.
[cited by applicant]
Cai et al., Variations in Template Protection by the RNA Polymerase II Transcription Complex During the Initiation Process, Molecular and Cellular Biology, vol. 7, No. 10, Oct. 1987, pp. 3371-3379.
[cited by applicant]
Canaani et al., Sequence Heterogeneity at the 5′ Termini of Late Simian Virus 40 19S and 16S mRNAs, The Proceedings of the National Academy of Sciences, vol. 76, No. 7, Jul. 1979, pp. 3078-3082.
[cited by applicant]
Carpousis et al., Cycling of Ribonucleic Acid Polymerase to Produce Oligonucleotides During Initiation in Vitro at the Lac UV5 Promoter, Biochemistry, vol. 19, No. 14, Jul. 8, 1980, pp. 3245-3253.
[cited by applicant]
Carpousis et al., Interaction of RNA Polymerase With lacUV5 Promoter DNA During mRNA Initiation and Elongation: Footprinting, Methylation, and Rifampicin-Sensitivity Changes Accompanying Transcription Initiation, Journa…
[cited by applicant]
Cazenave et al., RNA Template-Directed RNA Synthesis by T7 RNA Polymerase, Proceedings of the National Academy of Sciences of the United States of America, vol. 91, No. 15, Jul. 19, 1994, pp. 6972-6976.
[cited by applicant]
Chamberlin et al., Characterization of T7-Specific Ribonucleic Acid Polymerase I. General Properties of the Enzymatic Reaction and the Template Specificity of the Enzyme, Journal of Biological Chemistry, vol. 248, No. 6…
[cited by applicant]
Chiu et al., Tat Stimulates Cotranscriptional Capping of HIV mRNA, Journal of Molecular Cell, vol. 10, No. 3, Sep. 2002, pp. 585-597.
[cited by applicant]
Chu et al., Paradoxical Observations on the 5′Terminus of Ovalbumin Messenger Ribonucleic Acid, The Journal of Biological Chemistry, vol. 253, No. 15, Aug. 10, 1978, pp. 5228-5231.
[cited by applicant]
Chinese Application No. 201680067458.6, Office Action mailed on Feb. 7, 2021, 18 pages (8 pages of Original Document and 10 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Office Action mailed on Apr. 15, 2022, 27 pages (11 pages of Original Document and 16 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Office Action mailed on Jul. 4, 2023, 29 pages (12 pages of Original Document and 17 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Office Action mailed on Mar. 7, 2023, 8 pages (4 pages of Original Document and 4 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Office Action mailed on Sep. 20, 2022, 8 pages (3 pages of Original Document and 5 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Dec. 1, 2021, 10 pages.
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Nov. 8, 2021, 10 pages.
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Sep. 26, 2019, 2 pages.
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Jun. 16, 2023, 20 pages (10 pages of Original Document and 10 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Jun. 15, 2023, 24 pages (12 pages of Original Document and 12 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Jun. 20, 2023, 24 pages (12 pages of Original Document and 12 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Mar. 2, 2023, 30 pages (16 pages of Original Document and 14 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Jun. 21, 2023, 34 pages (17 pages of Original Document and 17 pages of English Translation).
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Dec. 17, 2021, 4 pages.
[cited by applicant]
Chinese Application No. 201680067458.6, Third Party Opinion mailed on Sep. 16, 2021, 5 pages.
[cited by applicant]
Chinese Application No. 202110537080.4, Office Action mailed on Mar. 14, 2023, 12 pages (5 pages of Original Document and 7 pages of English Translation).
[cited by applicant]
Chinese Application No. 202110537080.4, Office Action mailed on May 27, 2022, 13 pages (7 pages of Original Document and 6 pages of English Translation).
[cited by applicant]
Chinese Application No. 202110537080.4, Third Party Opinion mailed on Mar. 31, 2022, 10 pages.
[cited by applicant]
Chinese Application No. 202110537080.4, Third Party Opinion mailed on Jul. 18, 2023, 23 pages (13 pages of Original Document and 10 pages of English Translation).
[cited by applicant]
Chinese Application No. 202110537080.4, Third Party Opinion mailed on Mar. 20, 2023, 23 pages (12 pages of Original Document and 11 pages of English Translation).
[cited by applicant]
Chinese Application No. 202110537080.4, Third Party Opinion mailed on Dec. 1, 2021, 8 pages.
[cited by applicant]
Coleman et al., Superior 5′ Homogeneity of RNA from ATP-Initiated Transcription Under the T7 $2.5 Promoter, Nucleic Acids Research, vol. 32, No. 1, Jan. 15, 2004, pp. 1-4.
[cited by applicant]
Contreras et al., Simple, Efficient in Vitro Synthesis of Capped RNA Useful for Direct Expression of Cloned Eukaryoti Genes, Nucleic Acids Research, vol. 10, No. 20, Oct. 25, 1982, pp. 6353-6362.
[cited by applicant]
Crey-Desbiolles et al., Hybridization Properties and Enzymatic Replication of Oligonucleotides Containing the Photocleavable 7-nitroindole Base Analog, Nucleic Acids Research, vol. 33, No. 5, Mar. 1, 2005, pp. 1532-1543.
[cited by applicant]
Damase et al., The Limitless Future of RNA Therapeutics, Frontiers in Bioengineering and Biotechnology, vol. 9, Article 628137, Mar. 18, 2021, pp. 1-24.
[cited by applicant]
Dunn et al., Complete Nucleotide Sequence of Bacteriophage T7 DNA and the Locations of T7 Genetic Elements, Journal of Molecular Biology, vol. 166, Jun. 5, 1983, pp. 477-535.
[cited by applicant]
Egloff et al., An RNA Cap (Nucleoside-2′-o-)-Methyltransferase in the Flavivirus RNA Polymerase NS5: Crystal Structure and Functional Characterization, The European Molecular Biology Organization Journal, vol. 21, No. 1…
[cited by applicant]
European Application No. 16849423.5, Extended European Search Report mailed on Feb. 25, 2019, 10 pages.
[cited by applicant]
European Application No. 16849423.5, Notice of Decision to Grant mailed on Apr. 15, 2021, 2 pages.
[cited by applicant]
European Application No. 16849423.5, Notice of Opposition mailed on Feb. 25, 2022, 2 pages.
[cited by applicant]
European Application No. 16849423.5, Notice of Opposition mailed on Feb. 16, 2022, 54 pages.
[cited by applicant]
European Application No. 16849423.5, Notice of Opposition mailed on Feb. 17, 2022, 94 pages.
[cited by applicant]
European Application No. 16849423.5, Office Action mailed on Mar. 13, 2020, 7 pages.
[cited by applicant]
European Application No. 16849423.5, Office Action mailed on Oct. 25, 2019, 7 pages.
[cited by applicant]
European Application No. 16849423.5, Response to Oppositions mailed on Jul. 6, 2022, 45 pages.
[cited by applicant]
European Application No. 16849423.5, Summons to Attend Oral Proceedings mailed on Sep. 26, 2022, 30 pages.
[cited by applicant]
European Application No. 16849423.5, Third Party Observations mailed on Sep. 10, 2020, 40 Pages.
[cited by applicant]
European Application No. 21173131.0, Extended European Search Report mailed on Jan. 14, 2022, 12 pages.
[cited by applicant]
European Application No. 21173131.0, Office Action mailed on Jan. 27, 2023, 6 pages.
[cited by applicant]
European Application No. 21173142.7, Extended European Search Report mailed on Jan. 14, 2022, 12 pages.
[cited by applicant]
European Application No. 21173142.7, Office Action mailed on Jun. 14, 2023, 4 pages.
[cited by applicant]
European Application No. 21173142.7, Office Action mailed on Jan. 27, 2023, 5 pages.
[cited by applicant]
European Application No. 21173142.7, Office Action mailed on Aug. 10, 2022, 8 pages.
[cited by applicant]
European Application No. 21173278.9, Extended European Search Report mailed on Aug. 20, 2021, 12 pages.
[cited by applicant]
European Application No. 21173278.9, Office Action mailed on Jan. 27, 2023, 4 pages.
[cited by applicant]
European Application No. 21173278.9, Office Action mailed on Jun. 14, 2023, 5 pages.
[cited by applicant]
European Application No. 21173278.9, Office Action mailed on Aug. 10, 2022, 8 pages.
[cited by applicant]
European Application No. 22175377.5, Extended European Search Report mailed on Nov. 15, 2022, 6 pages.
[cited by applicant]
European Application No. 22175377.5, Office Action mailed on Jun. 14, 2023, 5 pages.
[cited by applicant]
European Application No. 22175377.5, Office Action mailed on Nov. 25, 2022, 7 pages.
[cited by applicant]
European Application No. 22190426.1, European Search Report mailed on Feb. 1, 2023, 8 pages.
[cited by applicant]
European Application No. 22190426.1, Intention to Grant mailed on Aug. 4, 2023, 9 pages.
[cited by applicant]
European Application No. 22190426.1, Office Action mailed on Mar. 13, 2023, 6 pages.
[cited by applicant]
Fechter et al, Ribozyme Processed tRNA Transcripts with Unfriendly Internal Promoter for T7 RNA Polymerase: Production and Activity, FEBS Letter, vol. 436, No. 1, 1998, pp. 99-103.
[cited by applicant]
Filipowicz, Functions of the 5′-Termnal m7G Cap in Euaryotic mRNA, Federation of Experimental Biologists Society Letter, vol. 96, No. 1, Dec. 1978, 11 pages.
[cited by applicant]
Freier et al., Improved Free-Energy Parameters for Predictions of RNA Duplex Stability, Proceedings of the National Academy of Sciences of the United States of America, vol. 83, No. 24, Dec. 1, 1986, pp. 9373-9377.
[cited by applicant]
Fukuoka et al., One-Pot Reaction for the Synthesis of m7G5′ pppG and m7G5′ pppA by Using an Activatable Bifunctional Phosphorylating Reagent, Tetrahedron Letters, vol. 35, No. 7, Feb. 14, 1994, pp. 1063-1066.
[cited by applicant]
Furuichi et al., 5′-Terminal Structure and mRNA Stability, Reprinted from Nature, vol. 266, No. 5599, Mar. 17, 1977, pp. 235-239.
[cited by applicant]
Gaur et al., Chemical and Enzymatic Approaches to Construct Modified RNAs, Methods of Molecular Biology, Ribozyme Protocols, vol. 74, 1997, pp. 99-110.
[cited by applicant]
Gaur et al., Combination of Chemical and Enzymatic RNA Synthesis, Methods in Molecular Biology, Ribozymes and siRNA Protocols, vol. 252, 2004, pp. 9-17.
[cited by applicant]
Gebhard et al., Functional RNA Elements in the Dengue Virus Genome, Viruses, vol. 3, No. 9, Sep. 15, 2011, pp. 1739-1756.
[cited by applicant]
Gingras et al., elF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of Translation, Annual Review of Biochemistry, vol. 68, No. 1, Jul. 1999, pp. 913-963.
[cited by applicant]
Gleghorn et al., X-ray Crystal Structures Elucidate the Nucleotidyl Transfer Reaction of Transcript Initiation Using Two Nucleotides, Proceedings of the National Academy of Sciences of the United States of America, vol.…
[cited by applicant]
Grudzien et al., Differential Inhibition of mRNA Degradation Pathways by Novel Cap Analogs, The Journal of Biological Chemistry, vol. 281, No. 4, Jan. 27, 2006, pp. 1857-1867.
[cited by applicant]
Grudzien-Nogalska et al., Synthesis of Anti-Reverse Cap Analogs (ARCAs) and their Applications in mRNA Translation and Stability, Methods in Enzymology, vol. 431, 2007, pp. 203-227.
[cited by applicant]
Gruegelsiepe et al., Enzymatic RNA Synthesis using Bacteriophage T7 RNA Polymerase, Handbook of RNA Biochemistry, Jan. 26, 2005, pp. 1-21.
[cited by applicant]
He et al., Phage RNA Polymerase Vectors That Allow Efficient Gene Expression in Both Prokaryotic and Eukaryotic Cells, Gene, vol. 164, No. 1, Oct. 16, 1995, pp. 75-79.
[cited by applicant]
Higman et al., The mRNA (Guanine-7-) Methyltransferase Domain of the Vaccinia Virus mRNA Capping Enzyme. Expression in
[cited by applicant]
Higman et al., The Vaccinia Virus mRNA (Guanine-N7-)-methyltransferase Requires Both Subunits of the mRNA Capping Enzyme for Activity, Journal of Biological Chemistry, vol. 267, No. 23, Aug. 15, 1992, pp. 16430-16437.
[cited by applicant]
Hill, Polymerase Recognition of Synthetic Oligodeoxyribonucleotides Incorporating Degenerate Pyrimidine and Purine Bases, Proceedings of the National Academy of Sciences, vol. 95, No. 8, Apr. 1998, pp. 4258-4263.
[cited by applicant]
Honcharenko et al., Synthesis and Evaluation of Stability of m3G-CAP Analogues in Serum-Supplemented Medium and Cytosolic Extract, Bioorganic & Medicinal Chemistry, vol. 21, No. 24, Dec. 15, 2013, pp. 7921-7928.
[cited by applicant]
Ikeda et al., Interactions of the RNA Polymerase of Bacteriophage T7 With Its Promoter During Binding and Initiation of Transcription, Proceedings of the National Academy of Sciences, vol. 83, No. 11, Jun. 1986, pp. 361…
[cited by applicant]
Imburgio et al., Studies of Promoter Recognition and Start Site Selection by T7 RNA Polymerase Using a Comprehensive Collection of Promoter Variants, Biochemistry, vol. 39, No. 34, Aug. 29, 2000, pp. 10419-10430.
[cited by applicant]
Ishikawa et al., Preparation of Eukaryotic mRNA Having Differently Methylated Adenosine at the 5′-Terminus and the Effect of the Methyl Group in Translation, Nucleic Acids Symposium Series, vol. 53, No. 1, Sep. 27, 2009…
[cited by applicant]
Jemielity et al., Novel “Anti-Reverse” Cap Analogs with Superior Translational Properties, RNA, vol. 9, No. 9, Sep. 2003, pp. 1108-1122.
[cited by applicant]
Japanese Application No. 2018-515136, Notice of Allowance mailed on Nov. 10, 2020, 4 pages (3 pages of Original Document and 1 page of English Translation).
[cited by applicant]
Japanese Application No. 2018-515136, Office Action mailed on Nov. 12, 2019, 6 pages (4 pages of Original Document and 2 pages of English Translation).
[cited by applicant]
Japanese Application No. 2020-204713, Notice of Allowance mailed on May 17, 2022, 4 pages (3 pages of Original Document and 1 page of English Translation).
[cited by applicant]
Japanese Application No. 2020-204713, Office Action mailed on Jan. 11, 2022, 9 pages (5 pages of Original Document and 4 pages of English Translation).
[cited by applicant]
Japanese Application No. 2022-070512, Office Action mailed on Jun. 13, 2023, 18 pages (9 pages of Original Document and 9 pages of English Translation).
[cited by applicant]
Kadokura et al., Solid-phase synthesis of a 5′-terminal TMG-capped trinucleotide block of U1 snRNA, Tetrahedron Letters, vol. 42, Issue 50, Dec. 10, 2001, pp. 8853-8856.
[cited by applicant]
Kennedy et al., Mechanism for De Novo RNA Synthesis and Initiating Nucleotide Specificity by T7 RNA Polymerase, Journal of Molecular Biology, vol. 370, No. 2, Jul. 6, 2007, pp. 256-268.
[cited by applicant]
Khandelwal et al., A Phenomenological Model for Predicting Melting Temperatures of DNA Sequences, Public Library of Science One, vol. 5, No. 8, Aug. 2010, pp. 1-9.
[cited by applicant]
Kincaid et al., Exploration of Factors Driving Incorporation of Unnatural dNTPS Into DNA by Klenow Fragment (DNA Polymerase I) and DNA Polymerase A, Nucleic Acids Research, vol. 33 mailed on No. 8, May 6, 2005, pp. 2620…
[cited by applicant]
Kleineidam et al., Efficient Cleavage of Pre-tRANs by
[cited by applicant]
Kobelt et al., Cancer Gene Therapy in Gene Therapy of Cancer: Methods and Protocols, Methods in Molecular Biology, vol. 2521, (Springer Nature 2022), 2022, pp. 1-15.
[cited by applicant]
Kolchinsky et al., Analysis of SNPs and Other Genomic Variations Using Gel-Based Chips, Human Mutation, vol. 19, No. 4, Apr. 2002, pp. 343-360.
[cited by applicant]
Kore et al., An Efficient Process for Synthesis of 2′-O-methyl and 3′-O-methyl Guanosine from 2-aminoadenosine Using Diazomethane and the Catalyst Stannous Chloride, Nucleosides, Nucleotides, and Nucleic Acids, vol. 25,…
[cited by applicant]
Kore et al., An Industrial Process for Selective Synthesis of 7-methyl Guanosine 5′-diphosphate: Versatile Synthon for Synthesis of mRNA Cap Analogues, Nucleosides, Nucleotides, and Nucleic Acids, vol. 25, No. 3, Mar. 2…
[cited by applicant]
Kore et al., Synthesis and Application of 2′-Fluoro-Substituted Cap Analogs, Bioorganic & Medicinal Chemistry Letters, vol. 17, No. 19, Oct. 1, 2007, pp. 5295-5299.
[cited by applicant]
Koukhareva et al., 3′-Protected 2′-Deoxynucleoside 5′-Triphosphates as a Novel Tool for Heat-Triggered Activation of PCR, Collection Symposium Series, vol. 10, 2008, pp. 259-263.
[cited by applicant]
Koukhareva et al., 3′-Protected 2′-Deoxynucleoside 5′-Triphosphates as a Novel Tool for Heat-Triggered Activation of PCR, Analytical Chemistry, vol. 81, No. 12, Jun. 15, 2009, pp. 4955-4962.
[cited by applicant]
Koukhareva et al., Chemical Route to the Capped RNAs, Nucleosides Nucleotides & Nucleic Acids, vol. 23, No. 10, 2004, pp. 1667-1680.
[cited by applicant]
Kowalska et al., Synthesis and Characterization of mRNA Cap Analogs Containing Phosphorothioate Substitutions That Bind Tightly to elF4E and are Resistant to the Decapping Pyrophosphatase DcpS, RNA, vol. 14, No. 6, Jun.…
[cited by applicant]
Kowalska et al., Synthesis, Properties, and Biological Activity of Boranophosphate Analogs of the mRNA Cap: Versatile Tools for Manipulation of Therapeutically Relevant Cap-Dependent Processes, Nucleic Acids Research, v…
[cited by applicant]
Korean Application No. 10-2018-7010893, Notice of Decision to Grant mailed on Dec. 9, 2022, 3 pages.
[cited by applicant]
Korean Application No. 10-2018-7010893, Notice of Third-Party Submission mailed on Jan. 18, 2022, 38 pages (25 pages of Original Document and 13 pages of English Translation).
[cited by applicant]
Korean Application No. 10-2018-7010893, Office Action mailed on Jun. 30, 2022, 39 pages (20 pages of Original Document and 19 pages of English Translation).
[cited by applicant]
Korean Application No. 10-2018-7010893, Office Action mailed on Aug. 4, 2021, 3 pages.
[cited by applicant]
Korean Application No. 10-2018-7010893, Office Action mailed on Nov. 19, 2021, 4 pages (3 pages of Original Document and 1 page of English Translation).
[cited by applicant]
Korean Application No. 10-2018-7010893, Third Party Submission mailed on Apr. 27, 2022, 57 pages.
[cited by applicant]
Kuge et al., Cap Ribose Methylation of c-mos mRNA Stimulates Translation and Oocyte Maturation in Xenopus Laevis, Nucleic Acids Research, vol. 26, No. 13, Jul. 1, 1998, pp. 3208-3214.
[cited by applicant]
Kuzmine et al., Binding of the Priming Nucleotide in the Initiation of Transcription by T7 RNA Polymerase, Journal of Biological Chemistry, vol. 278, No. 5, Jan. 31, 2003, pp. 2819-2823.
[cited by applicant]
Lebedev et al., Hot Start PCR With Heat-Activatable Primers: A Novel Approach for Improved PCR Performance, Nucleic Acids Research, vol. 36, No. 20, Nov. 2008, 18 pages.
[cited by applicant]
Lebedev et al., The Chirality Problem in P-Substituted Oligonucleotides, Perspectives in Drug Discovery and Design, vol. 4, No. 1, Dec. 1996, pp. 17-40.
[cited by applicant]
Lescure et al., Efficient and Selective Initiation by Yeast RNA Polymerase B in a Dinucleotide-Primed Reaction, Nucleic Acids Research, vol. 9, No. 1, Jan. 1981, pp. 31-45.
[cited by applicant]
Li, Encyclopedia of Chinese University Students, Liaoning Education Press, Mar. 1996, 12 pages.
[cited by applicant]
Li et al., Synthesis, Properties, and Applications of Oligonucleotides Containing an RNA Dinucleotide Phosphorothiolate Linkage, Accounts of Chemical Research, vol. 44, No. 12, Dec. 20, 2011, pp. 1257-1269.
[cited by applicant]
Loakes, Survey and Summary: The Applications of Universal DNA Base Analogues, Nucleic Acids Research, vol. 29, No. 12, Jun. 15, 2001, pp. 2437-2447.
[cited by applicant]
Lodish et al., Molecular Cell Biology, 6th Edition, 2008, 13 pages.
[cited by applicant]
Martin et al., Processivity in Early Stages of Transcription by T7 RNA Polymerase, Biochemistry vol. 27, No. 11, May 31, 1988, pp. 3966-3974.
[cited by applicant]
Martin et al., Purification of mRNA Guanylyltransferase and mRNA (Guanine-7-) Methyltransferase from Vaccinia Virions, The Journal of Biological Chemistry, vol. 250, No. 24, Dec. 25, 1975, pp. 9322-9329.
[cited by applicant]
McGinness et al., Substitution of Ribonucleotides in the T7 RNA Polymerase Promoter Element, The Journal of Biological Chemistry, vol. 277, No. 4, Jan. 2002, pp. 2987-2991.
[cited by applicant]
Melton et al., Efficient in Vitro Synthesis of Biologically Active RNA and RNA Hybridization Probes from Plasmids Containing a Bacteriophage SP6 Promoter, Nucleic Acids Research, vol. 12, No. 18, Sep. 25, 1984, pp. 7035…
[cited by applicant]
Mikkola et al., Preparation and Properties of mRNA 5′-Cap Structure, Current Organic Chemistry, vol. 9, No. 10, Dec. 31, 2005, pp. 999-1022.
[cited by applicant]
Milligan et al., Oligoribonucleotide Synthesis Using T7 RNA Polymerase and Synthetic DNA Templates, Nucleic Acids Research, vol. 15, No. 21, Nov. 11, 1987, pp. 8783-8798.
[cited by applicant]
Milligan et al., Synthesis of Small RNAs Using T7 RNA Polymerase, Methods in Enzymology, vol. 180, 1989, pp. 51-62.
[cited by applicant]
Miracco, Introduction to mRNA as a Medicine, Moderna, RNA Chemical Biology/External Technology Investments, 2022, 31 pages.
[cited by applicant]
Miracco, Moderna—Introduction to mRNA as a Medicine, Tides USA 2022: Oligonucleotide & Peptide Therapeutics Conference, May 9, 2022, 1 page.
[cited by applicant]
Moreno et al., A Synthetic snRNA m3G-CAP Enhances Nuclear Delivery of Exogenous Proteins and Nucleic Acids, Nucleic Acids Research, vol. 37, No. 6, Apr. 2009, pp. 1925-1935.
[cited by applicant]
Morita et al., Synthesis of ENA Nucleotides and ENA Oligonucleotides, Current Protocols in Nucleic Acid Chemistry, vol. 72, Mar. 2018, 21 pages.
[cited by applicant]
Moroney et al., Abortive Products as Initiating Nucleotides During Transcription by T7 RNA Polymerase, Biochemistry, vol. 30, No. 42, Oct. 1, 1991, p. 10343-10349.
[cited by applicant]
Muthukrishnan et al., 5′-Terminal 7-Methylguanosine in Eukaryotic mRNA is Required for Translation, Nature, vol. 255, No. 5503, May 1, 1975, pp. 33-37.
[cited by applicant]
Myette et al., Domain Structure of the Vaccinia Virus mRNA Capping Enzyme Expression in
[cited by applicant]
Nam et al., Transcription Initiation Site Selection and Abortive Initiation Cycling of Phage SP6 RNA Polymerase, The Journal of Biological Chemistry, vol. 263, No. 34, Jun. 8, 1988, pp. 18123-18127.
[cited by applicant]
Nygaard et al., Formation and Properties of RNA-DNA Complexes, Journal of Molecular Biology, vol. 9, Jul. 1964, pp. 125-142.
[cited by applicant]
Ohkubo et al., Chemical Synthesis of U1 snRNA Derivatives, Organic Letters, vol. 15, No. 17, Aug. 16, 2013, pp. 4386-4389.
[cited by applicant]
Osborn et al., Improving siRNA Delivery In Vivo Through Lipid Conjugation, Nucleic Acid Therapeutics, vol. 28, No. 3, 2018, pp. 128-136.
[cited by applicant]
Owczarzy et al., Stability and Mismatch Discrimination of Locked Nucleic Acid-DNA Duplexes, Biochemistry, vol. 50, No. 43, Nov. 1, 2011, pp. 9352-9367.
[cited by applicant]
Pasquinelli et al., Reverse 5′ Caps in RNAs made in Vitro by Phage RNA Polymerases, RNA, vol. 1, No. 9, Nov. 1995, pp. 957-967.
[cited by applicant]
International Application No. PCT/US2016/052670, International Preliminary Report on Patentability mailed on Dec. 15, 2017, 14 pages.
[cited by applicant]
International Application No. PCT/US2016/052670, International Search Report and Written Opinion mailed on Jan. 27, 2017, 18 pages.
[cited by applicant]
Peyrane et al., High-Yield Production of Short GpppA-and 7MeGpppA-capped RNAs and HPLC-Monitoring of Methyltransfer Reactions at the Guanine-N7 and Adenosine-2′O Positions, Nucleic Acids Research, vol. 35, No. 4, Jan. 2…
[cited by applicant]
Pitulle et al., Initiator Oligonucleotides for the Combination of Chemical and Enzymatic RNA Synthesis, Gene, vol. 112, No. 1, Mar. 1, 1992, pp. 101-105.
[cited by applicant]
Preparata et al., DNA Sequencing by Hybridization Using Semi-Degenerate Bases, Journal of Computational Biology, vol. 11, No. 4, Aug. 2004, pp. 753-765.
[cited by applicant]
Qi, Biochemistry—For traditional Chinese Medicine and Acupuncture Majors, Shanghai Science and Technology Press, 1994, 10 pages.
[cited by applicant]
Rasmussen et al., In Vivo Transcriptional Pausing and Cap Formation on Three Drosophila Heat Shock Genes, Proceedings of the National Academy of Sciences of the United States of America, vol. 90, No. 17, Sep. 1, 1993, p…
[cited by applicant]
Ray et al., West Nile Virus 5′-Cap Structure is Formed by Sequential Guanine N-7 and Ribose 2′-O Methylations by Nonstructural Protein 5, Journal of Virology, vol. 80, No. 17, Sep. 2006, pp. 8362--8370.
[cited by applicant]
Reese et al., Oligo-and Poly-Nucleotides: 50 Years of Chemical Synthesis, Organic & Biomolecular Chemistry, vol. 3, No. 21, Oct. 5, 2005, pp. 3851-3868.
[cited by applicant]
Rhoads, Signal Transduction Pathways That Regulate Eukaryotic Protein Synthesis, The Journal of Biological Chemistry, vol. 274, No. 43, Oct. 22, 1999, 30337-30340.
[cited by applicant]
Roberts et al., Advances in Oligonucleotide Drug Delivery, Nature Reviews Drug Discovery, vol. 19, Aug. 11, 2020, pp. 673-694.
[cited by applicant]
Rosa, Four T7 RNA Polymerase Promoters Contain an Identical 23 BP Sequence, Cell, vol. 16, No. 4, Apr. 1979, pp. 815-825.
[cited by applicant]
Rydzik et al., Synthesis and Properties of mRNA Cap Analogs Containing Imidodiphosphate Moiety—Fairly Mimicking Natural Cap Structure, Yet Resistant to Enzymatic Hydrolysis, Bioorganic & Medicinal Chemistry, vol. 20, No…
[cited by applicant]
Sahin et al., BNT162b2 Vaccine Induces Neutralizing Antibodies and Poly-specific T Cells in Humans, Nature, vol. 595, No. 7868, Jul. 22, 2021, pp. 572-577.
[cited by applicant]
Sahin et al., mRNA-Based Therapeutics—Developing a New Class of Drugs, Nature Reviews Drug Discovery, vol. 13, No. 10, Oct. 2014, pp. 759-780.
[cited by applicant]
Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, 3rd Edition, vols. 1, 2 and 3, 2001, 18 pages.
[cited by applicant]
Sawai et al., Synthesis and Reactions of Nucleoside 5′-Diphosphate Imidazolide. A Nonenzymatic Capping Agent for 5′-Monophosphorylated Oligoribonucleotides in Aqueous Solution, The Journal of Organic Chemistry, vol. 64,…
[cited by applicant]
Seelig et al., Ternary Conjugates of Guanosine Monophosphate as Initiator Nucleotides for the Enzymatic Synthesis of 5′-Modified RNAs, Bioconjugate Chem. vol. 10, May-Jun. 1999, pp. 371-378.
[cited by applicant]
Selisko et al., Biochemical Characterization of the (Nucleoside-2′ O)-Methyltransferase Activity of Dengue Virus Protein NS5 Using Purified Capped RNA Oligonucleotides 7MeGpppACn and GpppACn, Journal of General Virology…
[cited by applicant]
Senthilvelan et al., Trinucleotide Cap Analogue Bearing a Locked Nucleic Acid Moiety: Synthesis, mRNA Modification, and Translation for Therapeutic Applications, Organic Letters, American Chemical Society, vol. 23, No. …
[cited by applicant]
Senthilvelan et al., Trinucleotide Cap Analogue Bearing a Locked Nucleic Acid Moiety: Synthesis, mRNA Modification, and Translation for Therapeutic Applications, Organic Letters, vol. 23, May 19, 2021, pp. 4136-4136.
[cited by applicant]
Shatkin, Capping of Eucaryotic mRNAs, Cell, vol. 9, No. 4, Dec. 1976, pp. 645-653.
[cited by applicant]
Shatkin, mRNA Cap Binding Proteins: Essential Factors for Initiating Translation, Cell, vol. 40, No. 2, Feb. 1985, pp. 223-224.
[cited by applicant]
Shi, Basics of Molecular Biology, People's Medical Publishing House, Nov. 2000, 14 pages.
[cited by applicant]
Shigdar et al., Aptamers as Theranostic Agents: Modifications, Serum Stability and Functionalisation, Sensors, vol. 13, No. 10, Oct. 10, 2013, pp. 13624-13637.
[cited by applicant]
Shuman, Capping Enzyme in Eukaryotic mRNA Synthesis1, Progress in Nucleic Acid Research and Molecular Biology, vol. 50, 1995, pp. 101-129.
[cited by applicant]
Shuman et al., Purification and Characterization of a GTP-Pyrophosphate Exchange Activity from Vaccinia Virions. Association of the GTP-Pyrophosphate Exchange Activity with Vaccinia mRNA Guanylyltransferase. RNA (Guanin…
[cited by applicant]
Shuman, Structure, Mechanism, and Evolution of the mRNA Capping Apparatus, Progress Nucleic Acid Research Molecular Biology, vol. 66, 2000, pp. 1-40.
[cited by applicant]
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, vol. 48, No. 4, Jan. 27, 2020, pp.…
[cited by applicant]
Smith et al., A Unique Class of Compound, Guanosine-Nucleoside Tetraphosphate G(5′)pppp(5′)N, Synthesized During the in Vitro Transcription of Cytoplasmic Polyhedrosis Virus of Bombyx Mori—Structural Determination and M…
[cited by applicant]
Sokolov et al., A Rapid and Simple PCR-Based Method for Isolation of cDNAs from Differentially Expressed Genes, Nucleic Acids Research, vol. 22, No. 19, Sep. 25, 1994, pp. 4009-4015.
[cited by applicant]
Soler-Bistue et al., Bridged Nucleic Acids Reloaded, Molecules, vol. 24, No. 12, Jun. 2019, 17 pages.
[cited by applicant]
Sonenberg, Cap-Binding Proteins of Eukaryotic Messenger RNA: Functions in Initiation and Control of Translation, Progress in Nucleic Acid Research and Molecular Biology, vol. 35, 1988, pp. 173-207.
[cited by applicant]
Stec et al., Stereocontrolled Synthesis of Oligo (Nucleoside Phosphorothioate)s, Angewandte Chemie International Edition, vol. 33, No. 7, Apr. 18, 1994, pp. 709-722.
[cited by applicant]
Stepinski et al., Synthesis and Properties of mRNAs Containing the Novel “anti-reverse” Cap Analogs 7-methyl (3′-O-Methyl) GpppG and 7-methyl (3′-Deoxy) GpppG, RNA, vol. 7, No. 10, Oct. 2001, pp. 1486-1495.
[cited by applicant]
Taverniti et al., Elimination of Cap Structures Generated by mRNA Decay Involves the New Scavenger mRNA Decapping Enzyme Aph1/FHIT together With DcpS, Nucleic Acids Research, vol. 43, No. 1, Nov. 2014, pp. 482-492.
[cited by applicant]
Tekes et al., A Freeze Frame View of Vesicular Stomatitis Virus Transcription Defines a Minimal Length of RNA for 5′ Processing, PLoS Pathogens, vol. 7, No. 6, Jun. 2011, 11 pages.
[cited by applicant]
Thillier et al., Synthesis of 5′ Cap-0 and Cap-1 RNAs using Solid-Phase Chemistry Coupled with Enzymatic Methylation by Human (Guanine-N7)-Methyl Transferase, RNA, vol. 18, No. 4, Feb. 14, 2012, pp. 856-868.
[cited by applicant]
Van Den Elzen et al., mRNA 5′ Terminal Sequences Drive 200-Fold Differences in Expression Through Effects on Synthesis, Translation and Decay, Available Online at: https://www.biorxiv.org/content/10.1101/2022.02.17.4808…
[cited by applicant]
Waldner et al., Hydrophobic Effects in Duplexes with Modified Oligonucleotide Backbones and RNA, Bioorganic & Medicinal Chemistry Letters, vol. 6, No. 19, Oct. 8, 1996, pp. 2363-2366.
[cited by applicant]
Wang et al., Phylogeny of mRNA Capping Enzymes, Proceedings of the National Academy of Sciences, vol. 94, No. 18, Sep. 1997, pp. 9573-9578.
[cited by applicant]
Warminski et al., Structural Insights into the Interaction of Clinically Relevant Phosphorothioate mRNA Cap Analogs with Translation Initiation Factor 4E Reveal Stabilization via Electrostatic Thio-Effect, Warsaw, ACS C…
[cited by applicant]
Werner et al., 2′-o-ribose Methylation of Cap2 in Human: Function and Evolution in a Horizontally Mobile Family, Nucleic Acids Research, vol. 39, No. 11, Feb. 9, 2011, pp. 4756-4768.
[cited by applicant]
Westman et al., Removal of t-butyldimethylsilyl Protection in RNA-Synthesis. Triethylamine Trihydrofluoride (TEA, 3HF) is a more Reliable Alternative to Tetrabutylammonium Fluoride (TBAF), Nucleic Acids Research, vol. 2…
[cited by applicant]
Worch et al., Novel Way of Capping mRNA Trimer and Studies of its Interaction with Human Nuclear Cap-Binding Complex, Nucleosides, Nucleotides and Nucleic Acids, vol. 24, No. 5-7, Feb. 2005, pp. 1131-1134.
[cited by applicant]
Yamaguchi et al., Chemical Synthesis of The 5′-Terminal Part Bearing Cap Structure Of Messenger RNA Of Cytoplasmic Polyhedrosis Virus (CPV) m7G5′pppAmpG And m7G5′pppAmpGpU, Nucleic Acids Research, vol. 12, No. 6, Mar. 2…
[cited by applicant]
Yamakawa et al., Excess Synthesis of Viral mRNA 5′-Terminal Oligonucleotides by Reovirus Transcriptase, Journal of Biological Chemistry, vol. 256, No. 12, Jun. 25, 1981, pp. 6507-6514.
[cited by applicant]
Yisraeli et al., [4] Synthesis of Long, Capped Transcripts in Vitro by SP6 and T7 RNA Polymerases, Methods in Enzymology, vol. 180, 1989, pp. 42-50.
[cited by applicant]
Yong, Basics of Food Molecular Biology, China Light Industry Press, Aug. 2008, 12 pages.
[cited by applicant]
Ziemniak et al., Phosphate-Modified Analogues of m7GTP and m7Gppppm7G—Synthesis and Biochemical Properties, Bioorganic & Medicinal Chemistry, vol. 23, No. 17, Sep. 1, 2015, pp. 5369-5381.
[cited by applicant]
Zuberek et al., Phosphorylation of elF4E Attenuates its Interaction with mRNA 5′ Cap Analogs by Electrostatic Repulsion: Intein-Mediated Protein Ligation Strategy to Obtain Phosphorylated Protein, RNA, vol. 9, No. 1, Ja…
[cited by applicant]
Zytek et al., Towards Novel Efficient and Stable Nuclear Import Signals: Synthesis and Properties of Trimethylguanosine Cap Analogs Modified within the 5′,5′-Triphosphate Bridge, Organic & Biomolecular Chemistry, vol. 1…
[cited by applicant]
Canadian Application No. CA2,999,274 , “Notice of Allowance”, Oct. 29, 2021.
[cited by applicant]
Canadian Application No. CA2,999,274 , “Notice of Allowance”, Oct. 6, 2023, 1 page.
[cited by applicant]
Canadian Application No. CA2,999,274 , “Office Action”, Jul. 31, 2023, 4 pages.
[cited by applicant]
European Application No. EP16849423.5 , “Summons to Attend Oral Proceedings”, Sep. 11, 2023, 5 pages.
[cited by applicant]
European Application No. EP21173142.7 , “Intention to Grant”, Sep. 29, 2023, 9 pages.
[cited by applicant]
European Application No. EP21173278.9 , “Intention to Grant”, Sep. 29, 2023, 9 pages.
[cited by applicant]
Chinese Application No. CN202311200887.4, “Third Party Opinion”, Feb. 5, 2024, 16 pages (8 pages of Original Document and 8 pages of English Translation).
[cited by applicant]
Chinese Application No. CN202311200887.4, “Third Party Opinion”, Feb. 28, 2024, 10 pages (5 pages of Original Document and 5 pages of English Translation).
[cited by applicant]
Japanese Application No. JP2022-070512 , “Office Action”, Feb. 27, 2024, 21 pages (9 pages of Original Document and 12 pages of English Translation).
[cited by applicant]
Korean Application No. KR10-2023-7004950 , “Notice of Decision to Grant”, Feb. 25, 2024, 3 pages (3 pages of Original Document).
[cited by applicant]
Douglas, et al., “Inhibition of Respiratory Syncytial Virus Fusion by the Small Molecule VP-14637 via Specific Interactions with F Protein”, Journal of Virology, vol. 77, No. 9, May 2003, pp. 5054-5064.
[cited by applicant]
Moss, et al., “New mammalian expression vectors”, Nature, vol. 348, Nov. 1, 1990, pp. 91-92.
[cited by applicant]
Ikeda, et al., “T7 promoter contacts essential for promoter activity in vivo”, Nucleic Acids Research, vol. 20, No. 10, 1992, pp. 2517-2524.
[cited by applicant]
U.S. Appl. No. 18/408,431 , “Non-Final Office Action”, Apr. 11, 2024, 12 pages.
[cited by applicant]
U.S. Appl. No. 18/467,224 , “U.S Patent Application No.”, Compositions and Methods for Synthesizing 5′-Capped RNAs, Sep. 14, 2023, 106 pages.
[cited by applicant]
Chinese Application No. CN202311200887.4 , “Office Action”, Apr. 27, 2024, 18 pages (8 pages of Original Document and 10 pages of English Translation).
[cited by applicant]
European Application No. EP22190426.1 , “Notice of Opposition”, Apr. 18, 2024, 7 pages.
[cited by applicant]
European Application No. EP22190426.1 , “Third Party Observation”, Mar. 22, 2024, 2 pages.
[cited by applicant]
Australian Application No. AU2023201915, “First Examination Report”, May 17, 2024, 2 pages.
[cited by applicant]
Chinese Application No. CN202211046591.7, Third Party Opinion, Mar. 15, 2024, 41 pages (20 pages of Original Document and 21 pages of English Translation).
[cited by applicant]
European Application No. EP22190426.1 , “Notice of Opposition”, Jun. 12, 2024, 99 pages.
[cited by applicant]
Suzuki , et al., “Diverse Transcriptional Initiation Revealed by Fine Large-scale Mapping of mRNA Start Sites”, European Molecular Biology Organization Reports, vol. 2, No. 5, Mar. 1, 2001, pp. 388-393.
[cited by applicant]
European Application No. EP21173131.0 , “Office Action”, Mar. 21, 2024, 5 pages.
[cited by applicant]
“Capping Efficiency Comparison: −1+1 vs. claimed +1+2 hybridization”, Experimental Report, pp. 1-6.
[cited by applicant]
“Capping Efficiency Comparison: −1+1 vs. claimed +1+2 hybridization”, Supplementary Experimental Report, pp. 1-7.
[cited by applicant]
European Patent No. 3352584, “Decision Revoking the European Patent”, Apr. 11, 2024, pp. 1-25.
[cited by applicant]
“PGEM®-4Z Vector”, Technical Bulletin, Promega, May 2009, pp. 1-8.
[cited by applicant]
Liau , “mRNA Capping Analysis Report—Dinucleotide vs. Trinucleotide Cap Analogs”, Genetic Design & Manufacturing, Jun. 5, 2024, pp. 1-19.
[cited by applicant]
European Application No. EP23192203.0 , Office Action, Jun. 5, 2024, 4 pages.
[cited by applicant]
Chinese Application No. CN202110537080.4 , “Office Action”, May 25, 2024, 21 pages (10 pages of Original Document and 11 pages of English Translation).
[cited by applicant]
U.S. Appl. No. 18/408,431 , Notice of Allowance, Mailed On Jul. 10, 2024, 5 pages.
[cited by applicant]
Australian Patent Application No. AU2023201915 , “Notice of Acceptance”, Jul. 12, 2024, 3 pages.
[cited by applicant]
Australian Patent Application No. AU2023229522 , “First Examination Report”, Jul. 5, 2024, 3 pages.
[cited by applicant]
Chinese Patent Application No. CN202311200887.4 , Office Action, Mailed On Sep. 7, 2024, 15 pages (8 pages of original language copy and 7 pages of English Translation).
[cited by applicant]
European Patent Application No. EP21173142.7 , “Notice of Opposition”, Sep. 5, 2024, 2 pages.
[cited by applicant]
European Patent Application No. EP21173142.7 , “Notice of Opposition”, Aug. 23, 2024, 74 pages.
[cited by applicant]
European Patent Application No. EP21173278.9 , “Notice of Opposition”, Sep. 5, 2024, 2 pages.
[cited by applicant]
European Patent Application No. EP21173278.9 , “Notice of Opposition”, Aug. 29, 2024, 70 pages.
[cited by applicant]
European Patent Application No. EP22190426.1 , “Notice of Opposition”, Jun. 27, 2024, 2 pages.
[cited by applicant]
European Patent Application No. EP24186081.6, “Extended European Search Report”, Sep. 23, 2024, 11 pages.
[cited by applicant]
Kulasegaran-Shylini et al., “Structural and Functional Elements of the Promoter Encoded by the 5′ Untranslated Region of the Venezuelan Equine Encephalitis Virus Genome”, Journal of Virology, vol. 83, No. 17, Sep. 2009,…
[cited by applicant]
Strauss et al., “Complete Nucleotide Sequence of the Genomic RNA of Sindbis Virus”, Virology, vol. 133, No. 1, Feb. 1984, pp. 92-110.
[cited by applicant]
Damha , et al., “Oligoribonucleotide synthesis: The silyl-phosphoramidite method”, Methods in Molecular Biology, vol. 20, 1993, pp. 81-114.
[cited by applicant]
European Patent Application No. EP22175377.5 , “Notice of Opposition”, Oct. 30, 2024, 83 pages.
[cited by applicant]
Roy , et al., “Synthesis of DNA/RNA and Their Analogs via Phosphoramidite and H-Phosphonate Chemistries”, Molecules, vol. 18, No. 11, Nov. 18, 2013, pp. 14268-14284.
[cited by applicant]
Daube et al., “Functional Transcription Elongation Complexes from Synthetic RNA-DNA Bubble Duplexes”, Science, vol. 258, No. 5086, Nov. 20, 1992, pp. 1320-1324.
[cited by applicant]
European Patent Application No. EP22175377.5 , “Notice of Opposition”, Nov. 15, 2024, 2 pages.
[cited by applicant]
European Patent Application No. EP22175377.5 , “Notice of Opposition”, Nov. 5, 2024, 83 pages.
[cited by applicant]
European Patent Application No. EP23192203.0 , “Intention to Grant”, Nov. 28, 2024, 9 pages.
[cited by applicant]
European Patent Application No. EP23192203.0 , “Intention to Grant”, Dec. 17, 2024, 9 pages.
[cited by applicant]
Japanese Patent Application No. JP2022-070512 , Notice of Decision to Grant, Mailed On Nov. 12, 2024, 4 pages (1 page of English translation and 3 pages of official language copy).
[cited by applicant]
Kamzolova et al., “Electrostatic Map of T7 DNA. Comparative Analysis of Functional and Electrostatic Properties of T7 RNA Polymerase Specific Promoters”, Available online at: https://arxiv.org/pdf/1306.5228, Jun. 24, 20…
[cited by applicant]
Kore et al., “Chemical Synthesis of Dinucleotide Cap Analogs”, Current Protocols in Nucleic Acid Chemistry, vol. 55, No. 1, Dec. 2013, p. 13.13.1-13.13.12.
[cited by applicant]
Ziemniak et al., “Potential Therapeutic Applications of RNA Cap Analogs”, Future Medicinal Chemistry, vol. 5, No. 10, Jun. 1, 2013, pp. 1141-1172.
[cited by applicant]