Patent SG-11201811768W-A (SG)
Title: Modulation of tjp1 expression to regulate regeneration of heart cells
Inventor: HUNZIKER WALTER
IPC: A61K31/713
Filed: 2017-09-14
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property MD 1101111 0 DOI HIM 011101 0 011111111111111111111111111111111111111111111111 Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\"\"1 WO 2018/052374 Al 22 March 2018 (22.03.2018) W I PO I PC T (51) International Patent Classification: (72) Inventors: HUNZIKER, Walter; c/o Institute of Molec- A61K 31/713 (2006.01) A61P 9/10 (2006.01) ular and Cell Biology, 61 Biopolis Drive, Proteos, Singa- C12N 15/113 (2010.01) pore 138673 (SG). XU, Jianliang; c/o Institute of Molecu- (21) International Application Number: lar and Cell Biology, 61 Biopolis Drive, Proteos, Singapore PCT/SG2017/050462 138673 (SG). WANG, Jiong-Wei; Department of Surgery and Cardiovascular Research Institute (CVRI), NUS, Singa- (22) International Filing Date: pore, Centre for Translational Medicine, MD6, #08-01, 14 14 September 2017 (14.09.2017) Medical Drive, Singapore 117599 (SG). KAUSALYA, P. Jaya; c/o Institute of Molecular and Cell Biology, 61 Biopo- (25) Filing Language: English lis Drive, Proteos, Singapore 138673 (SG). (26) Publication Language: English (74) Agent: SPRUSON & FERGUSON (ASIA) PTE LTD; (30) Priority Data: P.O. Box 1531, Robinson Road Post Office, Singapore 10201607673U 14 September 2016 (14.09.2016) SG 903031 (SG). (71) Applicants: AGENCY FOR SCIENCE, TECHNOLO- (81) Designated States (unless otherwise indicated, for every — GY AND RESEARCH [SG/SG]; 1 Fusionopolis Way, kind of national protection available): AE, AG, AL, AM, #20-10 Connexis North Tower, Singapore 138632 (SG). AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, NATIONAL UNIVERSITY OF SINGAPORE [SG/SG]; CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 21 Lower Kent Ridge Road, Singapore 119077 (SG). 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, = Title: MODULATION OF TJP1 EXPRESSION TO REGULATE REGENERATION OF HEART CELLS (54) A = = 0 ZO-1 , GAPDH — = = = B = mTJP1 shRNA#1 --- SEQ ID NO: 3 CCGGCGTGGATTGAACTTACTAAATCTCGAGATTTAGTAAGTTCAATCCACGTTTITG = = mTSP1 shRNA#2 --- SEQ ID NO: 4 = — CCGGCCGCGAAGTTATGAGCAAGTTCTCGAGAACTTGCTCATAACTTCGCGGTTITTG = Figure 8 — ,-, 71' (57) : The invention is a method for treating a heart disease, in particular acute myocardial infarction (AMI) in a subject com- IN en prising the step of administering to the subject a Tjpl inhibitor, wherein administration of said Tjpl inhibitor promotes cardiomyocyte N proliferation. The invention further includes use of Tjpl inhibitor in the manufacture of a medicament for a heart disease, a patch, and In a nucleic acid encoding a Tjpl inhibitor. In a particular embodiment, the Tjpl inhibitor is a nucleic acid, i.e. an siRNA or shRNA of 0 ---, Tjp 1. The invention also includes administration of said Tjpl inhibitor in combination with Neuregulin-1 (NRG1 ), Fibroblast growth '1-1 a'C factor (FGF), Vascular endothelial growth factor (VEGF) or Follistatin-like 1 (Fst 1 ) and wherein said inhibitor is delivered in an C adeno-associated virus of serotype 9 (AAV 9). ei O [Continued on next page] WO 2018/052374 Al 11111111111111111110101011111 O11111O 111111111111111111111111111111111111111111 HOED MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 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: — of inventorship (Rule 4.17(iv)) Published: — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a))