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WO 2013/151667 Al 10 October 2013 (10.10.2013) P O P C T

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WO 2013/151667 Al 10 October 2013 (10.10.2013) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/151667 Al 10 October 2013 (10.10.2013) P O P C T (51) International Patent Classification: 61/681,720 10 August 2012 (10.08 2012) US C07H 21/00 (2006.01) 61/681,742 10 August 2012 (10.08 2012) US 61/681,649 10 August 2012 (10.08 2012) us (21) International Application Number: 61/681,645 10 August 2012 (10.08 2012) us PCT/US20 13/030063 61/681,661 10 August 2012 (10.08 2012) us (22) International Filing Date: 61/681,650 10 August 2012 (10.08 2012) us March 2013 (09.03.2013) 61/681,712 10 August 2012 (10.08 2012) us 61/696,381 4 September 2012 (04.09 2012) us (25) Filing Language: English 61/709,303 3 October 2012 (03 10 2012) us (26) Publication Language: English 61/712,490 11 October 2012 ( 11 10 2012) us 61/737,168 14 December 2012 (14 12 2012) us (30) Priority Data: 61/737,203 14 December 2012 (14 12 2012) us 61/618,862 2 April 2012 02.04 2012 US 61/737,155 14 December 2012 (14 12 2012) us 61/618,866 2 April 2012 02.04 2012 us 61/737,213 14 December 2012 (14 12 2012) us 61/618,868 2 April 2012 02.04 2012 us 61/737,134 14 December 2012 (14 12 2012) us 61/618,870 2 April 2012 02.04 2012 us 61/737,174 14 December 2012 (14 12 2012) us 61/618,873 2 April 2012 02.04 2012 us 61/737,139 14 December 2012 (14 12 2012) us 61/618,878 2 April 2012 02.04 2012 us 61/737,152 14 December 2012 (14 12 2012) us 61/618,885 2 April 2012 02.04 2012 us 61/737,184 14 December 2012 (14 12 2012) us 61/618,896 2 April 2012 02.04 2012 us 61/737,160 14 December 2012 (14 12 2012) us 61/618,91 1 2 April 2012 02.04 2012 us 61/737,135 14 December 2012 (14 12 2012) us 61/618,922 2 April 2012 02.04 2012 us 61/737,191 14 December 2012 (14 12 2012) us 61/618,935 2 April 2012 02.04 2012 us 61/737,130 14 December 2012 (14 12 2012) us 61/618,945 2 April 2012 02.04 2012 us 61/737,147 14 December 2012 (14 12 2012) us 61/618,953 2 April 2012 02.04 2012 us 61/618,961 2 April 2012 02.04 2012 us (71) Applicant: MODERNA THERAPEUTICS [US/US]; 61/618,957 2 April 2012 02.04 2012 us 161 First Street, First Floor, Cambrid ge, Massachusetts 61/648,286 17 May 2012 17.05 2012 us 02142 (US). 61/648,244 17 May 2012 17.05 2012 us (72) Inventors: BANCEL, Stephane; 68 Pinckney Road, Bo 61/668,157 5 July 2012 05.07 2012 us ston, Massachusetts 021 14 (US). CHAKRABORTY, 61/681,667 10 August 2012 10.08 2012 us Tirtha; 153 Woburn Street, Medford, Massachusetts 61/681,648 10 August 2012 10.08 2012 us 02155 (US). DE FOUGEROLLES, Antonin; 66 Summit 61/681,675 10 August 2012 10.08 2012 us Avenue, Brookline, Massachusetts 02446 (US). EL- 61/681,654 10 August 2012 10.08 2012 us BASHIR, Sayda M.; 149 Grove Street, Cambridge, Mas 61/681,687 10 August 2012 10.08 2012 us sachusetts 02138 (US). JOHN, Matthias; 338 Harvard St. 10 August 2012 10.08 2012 61/681,647 us #5, Cambridge, Massachusetts 02138 (US). ROY, Atanu; 61/681,696 10 August 2012 10.08 2012 us 115 Hill Street #9, Stoneham, Massachusetts 02180 (US). 61/681,658 10 August 2012 10.08 2012 us WHORISKEY, Susan; 47 Louise Road, Belmont, Mas 61/681,704 10 August 2012 10.08 2012 us sachusetts 02478 (US). WOOD, Kristy M.; 501 Huron [Continued on nextpage] (54) Title: MODIFIED POLYNUCLEOTIDES FIGURE 1 100 1 S 107 110 , a 104 03 106 (57) Abstract: Described herein are compositions, methods, processes, kits and devices for the design, preparation, manufacture and/or formulation of modified mRNA (mmRNA) molecules. The details of various embodiments of the invention are set forth in o the description below. Other features, objects, and advantages of the invention will be apparent from the description and the draw ings, and from the claims. The foregoing and other objects, features and advantages will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to o the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illus - trating the principles of various embodiments of the invention. w o 2013/151667 Ai llll II II 11III III I II II III II II III II I II Ave, Unit 2 , Cambridge, Massachusetts 02138 (US). RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, HAT ALA, Paul; 26 Monument Street #1, Charlestown, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, Massachusetts 02124 (US). SCHRUM, Jason P.; 4601 ZA, ZM, ZW. Flat Rock Road, Apt. 4 17, Philadelphia, Pennsylvania (84) Designated States (unless otherwise indicated, for every 19127 (US). EJEBE, Kenechi; 208 Pearl Street, Apt. 1, kind of regional protection available): ARIPO (BW, GH, Cambridge, Massachusetts 02139 (US). ELLSWORTH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, Jeff Lynn; 23 Meriam Street, Lexington, Massachusetts UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 02420 (US). GUILD, Justin; 495 Edgell Rd, Framing- TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, ham, Massachusetts 01701 (US). EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, (74) Agent: WARD, Donna T.; Dt Ward, P.C., 142A Main LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Street, Groton, Massachusetts 01450 (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, Published: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, — with international search report (Art. 21(3)) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, — before the expiration of the time limit for amending the GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, claims and to be republished in the event of receipt of KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, amendments (Rule 48.2(h)) MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, — with sequence listing part of description (Rule 5.2(a)) NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, MODIFIED POLYNUCLEOTIDES REFERENCE TO SEQUENCE LISTING [0001] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing file entitled M301_PCTSQLST.txt, was created on March 9, 2013 and is 104,018 bytes in size. The information in electronic format of the Sequence Listing is incorporated herein by reference in its entirety. CROSS REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to U.S. Provisional Patent Application No 61/681,742, filed, August 10, 2012, entitled Modified Polynucleotides for the Production of Oncology-Related Proteins and Peptides, U.S. Provisional Patent Application No 61/737,224, filed December 14, 2012, entitled Terminally Optimized Modified RNAs, International Application No PCT/US2012/069610, filed December 14, 2012, entitled Modified Nucleoside, Nucleotide, and Nucleic Acid Compositions, U.S. Provisional Patent Application No 61/618,862, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Biologies, U.S. Provisional Patent Application No 61/681,645, filed August 10, 2012, entitled Modified Polynucleotides for the Production of Biologies, U.S. Provisional Patent Application No 61/737,130, filed December 14, 2012, entitled Modified Polynucleotides for the Production of Biologies, U.S. Provisional Patent Application No 61/618,866, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Antibodies, U.S. Provisional Patent Application No 61/681,647, filed August 10, 2012, entitled Modified Polynucleotides for the Production of Antibodies, U.S. Provisional Patent Application No 61/737,134, filed December 14, 2012, entitled Modified Polynucleotides for the Production of Antibodies, U.S. Provisional Patent Application No 61/618,868, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Vaccines, U.S. Provisional Patent Application No 61/681,648, filed August 10, 2012, entitled Modified Polynucleotides for the Production of Vaccines, U.S. Provisional Patent Application No 61/737,135, filed December 14, 2012, entitled Modified Polynucleotides for the Production of Vaccines, U.S. Provisional Patent Application No 61/618,870, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Therapeutic Proteins and Peptides, U.S. Provisional Patent Application No 61/681,649, filed August 10, 2012, entitled Modified Polynucleotides for the Production of Therapeutic Proteins and Peptides, U.S. Provisional Patent Application No 61/737,139, filed December 14, 2012, Modified Polynucleotides for the Production of Therapeutic Proteins and Peptides, U.S. Provisional Patent Application No 61/618,873, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Secreted Proteins, U.S.
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