Patent SG-11201907916T-A (SG)
Title: Compounds and compositions for intracellular delivery of therapeutic agents
Inventor: BENENATO KERRY E
IPC: C07C335/08
Filed: 2018-03-15
Abstract: 1 Cr) O 1-1 00 1-1 O (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 20 September 2018 (20.09.2018) WIP0 I PCT omit VIII °nolo olomoiminoiliflo oimIE (10) International Publication Number WO 2018/170306 Al Fig. 400000 350000 300000 250000 200000 150000 100000 50000 (51) International Patent Classification: C07C 229/16 (2006.01) C07D 473/00 (2006.01) C07D 233/61 (2006.01) A61K 47/14 (2017.01) C07C 275/14 (2006.01) A61K 47/24 (2006.01) C07C 311/05 (2006.01) A61K 47/28 (2006.01) C07C 335/08 (2006.01) A61K 9/127 (2006.01) C07C 233/36 (2006.01) A61K 9/51 (2006.01) C07D 295/13 (2006.01) CO7D 249/04 (2006.01) CO7C 279/28 (2006.01) CO7C 259/06 (2006.01) CO7D 239/46 (2006.01) CO7C 307/06 (2006.01) (21) International Application Number: PCT/US2018/022717 (22) International Filing Date: 15 March 2018 (15.03.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/471,937 15 March 2017 (15.03.2017) US 62/475,140 22 March 2017 (22.03.2017) US (71) Applicant: MODERNATX, INC. [US/US]; 200 Technol- ogy Square, Cambridge, Massachusetts 02139 (US). (72) Inventors: BENENATO, Kerry E.; ModernaTX, Inc., 200 Technology Square, Cambridge, Massachusetts 02139 (US). KUMARASINGHE, Ellalahewage Sathyajith; ModernaTX, Inc., 200 Technology Square, Cambridge, Massachusetts 02139 (US). CORNEBISE, Mark; Moder- naTX, Inc., 200 Technology Square, Cambridge, Massachu- setts 02139 (US). (74) Agent: PEMBERTON, Christine C. et al.; Cooley LLP, 1299 Pennsylvania Avenue, NW, Suite 700, Washington, District of Columbia 20004-2400 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (54) Title: COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF THERAPEUTIC AGENTS hEPO (pg/mL i- ' I ,, .. 1 i A i____I. 1 [ --1 i is 11 ' Al 1 <IA m O .n Lila \"- o ' 2.22‘ .0 Day in 0 1 aaalaal it5 I Z' A, O!O A i o 2 aa 2 tr, 2 Day A 1 \"t7A oloo 2 8 si±n 0 al '00 - ,,,, N E. E \",\",5 ' ;5 oio E I E - g - 4 ,- N Day 15 aiaaaSaaaalaaaa,5aaLaaa 2 g ..Ar 00 E ic - 77' 7 ' E. . ' ' 0, ,, , '0, - ; E ) °- E A 4 ,2 L\": E - c., Fr '.- Day 22 Co N - 000 77 ‘L' \"7 F2 -,:', w 0 q MC3 0 hePO mRNA n MC3 111 iePO mRNA in MC31Methotrexate 3 hePO mRNA in MC3/Dexamettieson (57) : The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression. [Continued on next page] WO 2018/170306 Al MUNRO DOI 01011M1E1 010 HI 1101 110DEVOIS OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(U)) Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a))