(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 2013/151671 Al 10 October 2013 (10.10.2013) P O P C T (51) International Patent Classification: 61/681,704 10 August 2012 (10.08.2012) US A61K 31/7115 (2006.01) 61/681,720 10 August 2012 (10.08.2012) us 61/681,742 10 August 2012 (10.08.2012) us (21) International Application Number: 61/681,645 10 August 2012 (10.08.2012) us PCT/US20 13/030068 61/681,650 10 August 2012 (10.08.2012) us (22) International Filing Date: 61/681,661 10 August 2012 (10.08.2012) us March 2013 (09.03.2013) 61/681,648 10 August 2012 (10.08.2012) us 61/681,712 10 August 2012 (10.08.2012) us (25) Filing Language: English 61/696,381 4 September 2012 (04.09.2012) us (26) Publication Language: English 61/709,303 3 October 2012 (03. 10.2012) us 61/712,490 11 October 2012 ( 11.10.2012) us (30) Priority Data: 61/737,168 14 December 2012 (14. 12.2012) us 61/618,862 2 April 2012 (02.04.2012) US 61/737,203 14 December 2012 (14. 12.2012) us 61/618,866 2 April 2012 (02.04.2012) US 61/737,155 14 December 2012 (14. 12.2012) us 61/618,868 2 April 2012 (02.04.2012) us 61/737,213 14 December 2012 (14. 12.2012) us 61/618,870 2 April 2012 (02.04.2012) us 61/737,139 14 December 2012 (14. 12.2012) us 61/618,873 2 April 2012 (02.04.2012) us 61/737,174 14 December 2012 (14. 12.2012) us 61/618,878 2 April 2012 (02.04.2012) us 61/737,135 14 December 2012 (14. 12.2012) us 61/618,885 2 April 2012 (02.04.2012) us 61/737,152 14 December 2012 (14. 12.2012) us 61/618,896 2 April 2012 (02.04.2012) us 61/737,184 14 December 2012 (14. 12.2012) us 61/618,91 1 2 April 2012 (02.04.2012) us 61/737,160 14 December 2012 (14. 12.2012) us 61/618,922 2 April 2012 (02.04.2012) us 61/737,130 14 December 2012 (14. 12.2012) us 61/618,935 2 April 2012 (02.04.2012) us 61/737,191 14 December 2012 (14. 12.2012) us 61/618,945 2 April 2012 (02.04.2012) us 61/737,134 14 December 2012 (14. 12.2012) us 61/618,953 2 April 2012 (02.04.2012) us 61/737,147 14 December 2012 (14. 12.2012) us 61/618,961 2 April 2012 (02.04.2012) us 61/618,957 2 April 2012 (02.04.2012) us Applicant: MODERNA THERAPEUTICS [US/US]; 161 First Street, First Floor, Cambridge, MA 02142 (US). 61/648,286 17 May 2012 (17.05.2012) 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, MA 021 14 (US). HUANG, Eric, Yi-Chun; 90 Ware- 61/681,667 10 August 2012 (10.08.2012) us ham Street #302, Boston, MA 021 18 (US). 61/681,647 10 August 2012 (10.08.2012) us 61/681,675 10 August 2012 (10.08.2012) us (74) Agent: WARD, Donna, T.; DT WARD, P.C., 142A Main 61/681,654 10 August 2012 (10.08.2012) us Street, Groton, MA 01450 (US). 61/681,687 10 August 2012 (10.08.2012) us (81) Designated States (unless otherwise indicated, for every 10 August 2012 (10.08.2012) 61/681,649 us kind of national protection available): AE, AG, AL, AM, 61/681,696 10 August 2012 (10.08.2012) us AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 61/681,658 10 August 2012 (10.08.2012) us [Continued on nextpage] (54) Title: MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF COSMETIC PROTEINS AND PEPTIDES 100 Figure 1 108 n o (57) Abstract: Described herein are compositions, methods, processes, kits and devices for the design, preparation, manufacture and/or formulation of modified mRNA (mmRNA) molecules encoding at least one cosmetic polypeptide of interest. The present in o vention provides a method of treating a disease, disorder and/or condition in a subject in need thereof by increasing the level of at least one cosmetic polypeptide of interest comprising administering to said subject an isolated polynucleotide selected from the group consisting of SEQ ID NOs 884-161 1 and 5691-5707 comprising, a first region of linked nucleosides, said first region encod o ing the cosmetic polypeptide of interest, a first flanking region located at the 5' terminus of said first region comprising a sequence of linked nucleosides selected from the group consisting of the native 5' untranslated region (UTR). w o 2013/151671 A I llI II III ill III III III III BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, GW, ML, MR, NE, SN, TD, TG). RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, Published: ZA, ZM, ZW. — with international search report (Art. 21(3)) (84) Designated States (unless otherwise indicated, for every — with sequence listing part of description (Rule 5.2(a)) kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF COSMETIC PROTEINS AND PEPTIDES REFERENCE TO SEQUENCE LISTING [0001] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing file entitled MNCl_20SQLST.txt, created on March 09, 2013 which is 17,037,558 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. Provisional Patent Application No 61/681,650, filed August 10, 2012, entitled Modified Polynucleotides for the Production of Secreted Proteins, U.S. Provisional Patent Application No 61/737,147, filed December 14, 2012, entitled Modified Polynucleotides for the Production of Secreted Proteins, U.S. Provisional Patent Application No 61/618,878, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Plasma Membrane Proteins, U.S. Provisional Patent Application No 61/681,654, filed August 10, 2012, entitled Modified Polynucleotides for the Production of Plasma Membrane Proteins, U.S. Provisional Patent Application No 61/737,152, filed December 14, 2012, entitled Modified Polynucleotides for the Production of Plasma Membrane Proteins, U.S. Provisional Patent Application No 61/618,885, filed April 2, 2012, entitled Modified Polynucleotides for the Production of Cytoplasmic and Cytoskeletal Proteins, U.S.