(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 2018/206466 Al 15 November 2018 (15.11.2018) W ! P O PCT (51) International Patent Classification: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, A61K 31/403 (2006.01) A61K 31/424 (2006.01) KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, A61K 45/06 (2006.01) A61K 31/43 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, A61P 31/06 (2006.01) A61K 31/454 (2006.01) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, A61P 31/08 (2006.01) A61K 31/496 (2006.01) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, A61K 31/133 (2006.01) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (21) International Application Number: (84) Designated States (unless otherwise indicated, for every PCT/EP2018/061615 kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (22) International Filing Date: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 04 May 2018 (04.05.2018) TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (25) Filing Language: English 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, (26) Publication Langi English TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (30) Priority Data: KM, ML, MR, NE, SN, TD, TG). 17382255.2 08 May 2017 (08.05.2017) EP Declarations under Rule 4.17: (71) Applicants: GLAXOSMITHKLINE INTELLECTUAL — as to applicant's entitlement to apply for and be granted a PROPERTY DEVELOPMENT LIMITED [GB/GB]; patent (Rule 4.1 7(H)) 980 Great West Road, Brentford Middlesex TW8 9GS — as to the applicant's entitlement to claim the priority of the (GB). THE UNIVERSITY OF BRITISH COLUMBIA earlier application (Rule 4.17(Hi)) [CA/CA]; #103-6190 Agronomy Road, Vancouver, British Columbia V6T 1Z3 (CA). Published: — with international search report (Art. 21(3)) (72) Inventors: BARROS AGUIRRE, David; GlaxoSmithK- line, Severo Ochoa 2 Parque Tecnologico de Madrid, Tres Cantos, 28760 Madrid (ES). BATES, Robert H.; GlaxoSmithKline, Severo Ochoa 2 Parque Tecnologico de Madrid, Tres Cantos, 28760 Madrid (ES). GONZALEZ DEL RIO, Ruben; GlaxoSmithKline, Severo Ochoa 2 Par que Tecnologico de Madrid, Tres Cantos, 28760 Madrid (ES). MENDOZA LOSANA, Alfonso; GlaxoSmithKline, Severo Ochoa 2 Parque Tecnologico de Madrid, Tres Can tos, 28760 Madrid (ES). RAMON GARCIA, Santiago; Andador Luis Puntes 10, 4°B, 50008 Zaragoza (ES). (74) Agent: AHERN, Jenna Marie; GlaxoSmithKline, Global Patents (CN925. 1), 980 Great West Road, Brentford M id dlesex TW8 9GS (GB). (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, (54) Title: SANFETRINEM OR A SALT OR ESTER THEREOF FOR USE IN TREATING MYCOBACTERIAL INFECTION (57) Abstract: The present invention relates to formula (I) or a pharmaceutically ac ceptable salt or ester prodrug thereof for use in the treatment of a mycobacterial infec tion or disease resulting from a mycobacterial infection, such as tuberculosis. o (I) 00 o o SANFETRINEM OR A SALT OR ESTER THEREOF FOR USE IN TREATING MYCOBACTERIAL INFECTION The work leading to this invention has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291799. Field of the Invention The present invention relates to sanfetrinem, or a pharmaceutically acceptable salt or ester prodrug thereof, and its use in the treatment of a mycobacterial infection or a disease resulting from a mycobacterial infection. More specifically, the present invention relates to the use of sanfetrinem, or a pharmaceutically acceptable salt or ester prodrug thereof, in the treatment of tuberculosis. In particular, the present invention relates to the prodrug, sanfetrinem cilexetil, and its use in the treatment of tuberculosis. Background to the Invention Nearly ten million people are infected with tuberculosis (TB) each year, causing 1.5 million deaths each year, according to a report published by The World Health Organisation in 2014. Despite available treatments for tuberculosis, the global disease burden remains a major problem owing to Mycobacterium tuberculosis, the causative bacterial agent for TB, becoming resistant to many of the treatments. Although TB is caused by bacterial infection, the use of the most prominent class of antibiotics, the β-lactams, has been largely ignored. Despite the fact that the dozens of approved β- lactam drugs make up an estimated two thirds of the global antibiotic market, their evaluation against TB was limited by early failures in clinical trials and assumptions that the lypophilic mycobacterial cell wall was impermeable to such highly polar molecules. Sanfetrinem cilexetil is an experimental antibiotic from the 1990s linked with infections caused by a variety of bacterial species but not including mycobacteria. Owing to the ever-growing emergence of multi-drug resistant strains of Mycobacterium tuberculosis and continued high incidence of TB, there exists an urgent need to provide further drug compounds for the treatment of TB. Summary of the Invention In a first aspect of the present invention, there is provided , having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof for use in the treatment of a disease resulting from a mycobacterial infection. In a second aspect of the present invention, there is provided , having the name ( 1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof for use in the treatment of a mycobacterial infection. In a third aspect of the present invention, there is provided , having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof for use in the treatment of tuberculosis. In a fourth aspect of the present invention, there is provided a method for the treatment of a disease resulting from a mycobacterial infection in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of , having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof. In a fifth aspect of the present invention, there is provided a method for the treatment of a mycobacterial infection in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof. In a sixth aspect of the present invention, there is provided a method for the treatment of tuberculosis in a patient in need thereof, comprising administering a therapeutically effective amount of having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof. In a seventh aspect of the present invention, there is provided use of , having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof in the manufacture of a medicament for use in the treatment of tuberculosis, a mycobacterial infection or a disease resulting from a mycobacterial infection. In an eighth aspect of the present invention, there is provided a pharmaceutical composition comprising (a) , having the name ( 1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof; and (b) a pharmaceutically acceptable excipient, for use in the treatment of tuberculosis, a mycobacterial infection or a disease resulting from a mycobacterial infection. In a ninth aspect of the present invention, there is provided a combination of (a) having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof; and (b) a further other anti tuberculosis agent, for use in the treatment of a mycobacterial infection, a disease resulting from a mycobacterial infection, or tuberculosis. In a tenth aspect of the present invention, there is provided a combination of (a) having the name (1S,5S,8aS,8bR)-1-((R)-1-hydroxyethyl)-5- methoxy-2-oxo-1 ,2,5,6,7,8,8a,8b-octahydroazeto[2,1-a]isoindole-4-carboxylic acid, or a pharmaceutically acceptable salt or ester prodrug thereof; and (b) a β-lactamase inhibitor.