(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 2018/190970 Al 18 October 2018 (18.10.2018) W !P O PCT (51) International Patent Classification: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, CI2Q 1/32 (2006.01) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (21) International Application Number: EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, PCT/US2018/021 109 MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (22) International Filing Date: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 06 March 2018 (06.03.2018) KM, ML, MR, NE, SN, TD, TG). (25) Filing Language: English Declarations under Rule 4.17: (26) Publication Langi English — as to applicant's entitlement to apply for and be granted a patent (Rule 4.1 7(H)) (30) Priority Data: — as to the applicant's entitlement to claim the priority of the 62/484,141 11 April 2017 ( 11.04.2017) US earlier application (Rule 4.17(Hi)) (71) Applicant: REGENERON PHARMACEUTICALS, Published: INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, — with international search report (Art. 21(3)) New York 10591-6707 (US). — with sequence listing part of description (Rule 5.2(a)) (72) Inventors: STEVIS, Panayiotis; 777 Old Saw Mill Riv er Road, Tarrytown, New York 10591-6707 (US). ESOPI, David; 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 (US). GROMADA, Jesper; 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 (US). HALLER, Jorge; 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 (US). LIU, Yashu; 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 (US). MURPHY, Andrew; 777 Old Saw Mill River Road, New York, New York 10591-6707 (US). OLSON, William; 777 Old Saw Mill River Road, Tarry town, New York 10591-6707 (US). (74) Agent: LEGAARD, Paul K.; Stradley Ronon Stevens & Young, LLP, 30 Valley Stream Parkway, Malvern, Penn sylvania 19355-1481 (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, 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, © (54) Title: ASSAYS FOR SCREENING ACTIVITY OF MODULATORS OF MEMBERS OF THE HYDROXYSTEROID ( 17-BE TA) DEHYDROGENASE (HSD17B) FAMILY © (57) Abstract: Screening methods as well as kits for identifying modulators of hydroxysteroid (17-beta) dehydrogenase (HSD17B) family member proteins, such as HSD17B13, are provided. The methods comprise screemng molecules for their capacity to modulate the HSD17B family member protein, including inhibiting the HSD17B family member protein, as measured by substrate depletion, 00 product concentration from the HSD17B family member protein substrate conversion or NADH concentration, levels of labeled sub o strate, luciferin light emission, or combinations thereof. Inhibitors of HSD17B family member proteins identified through the screening methods may be used to treat liver diseases, disorders, or conditions in which the HSD 17B family member protein plays a role. ASSAYS FOR SCREENING ACTIVITY OF MODULATORS OF MEMBERS OF THE HYDROXYSTEROID (17-BETA) DEHYDROGENASE (HSD17B) FAMILY REFERENCE TO SEQUENCE LISTING This application includes a Sequence Listing filed electronica lly as a text file named 18923800102SEQ, created on Februa ry 10, 2018, with a size of 22 KB. The Sequence Listing is incorporated herein by refere nce. FIELD This disclosure relates genera lly t o the field of com pound screeni ng. More pa rticu la rly, the disclosu re re lates t o biochemica l and cel l-based assays in which molecu les or com positions are evaluated for their ca pacity t o mod ulate enzymatic activity of mem be rs of the hydroxysteroid (17- beta) dehydrogenase (HSD17B) family, especia lly their inhibitory ca pacity. BACKGROUND Various publications, including patents, patent applications, published patent applications, accession num be rs, technica l articles and schola rly articles are cited t hroughout the specification. Each of these cited publications is incorporated by reference, in its entirety and for all purposes, in this document. Chronic liver disease and cirrhosis are leading ca uses of morbidity and morta lity in the United States, accou nting for 38,170 deaths (1.5% of tota l deaths) in 2014. The most com mon etiologies of cirrhosis in the U.S. are alcoholic liver disease, chronic hepatitis C, and nona lcoholic fatty liver disease (NAFLD), together accounting for ~80% of patients awaiting liver tra nspla nt between 2004 and 2013. The estimated preva lence of NAFLD in the U.S. is between 19 and 46 and is risi ng over time, likely in conj unction with increased rates of obesity, its prima ry risk factor. Whi le significa nt adva nces have been made in the treatment of hepatitis C, there are curre ntly no evidence-based treatments for alcoholic or nona lcoholic liver disease and cirrhosis. SUMMARY In a first aspect of the disclosure, a method for screening a test compound for capability t o modulate one or more members of the hydroxysteroid (17-beta) dehydrogenase (HSD17B) family comprises contacting a first HSD17B family member protein with a test compound, a substrate for the HSD17B family member protein, NAD+ or NAD(P)+, a pre-reduced form of luciferin, an enzyme that reduces the pre-reduced form of luciferin t o produce luciferin, and luciferase, contacting a same second HSD17B family member protein with a control, a substrate for the HSD17B family member protein, NAD+ or NAD(P)+, a pre-reduced form of luciferin, an enzyme that reduces the pre-reduced form of luciferin t o produce luciferin, and luciferase, detecting the emission wavelength of luciferin produced, and identifying the test compound as an inhibitor of the HSD17B family member protein when the emission wavelength of luciferin produced in the presence of the test compound is lower than the wavelength of luciferin produced in the presence of the control, or identifying the test compound as an activator of the HSD17B family member protein when the emission wavelength of luciferin produced in the presence of the test compound is higher than the wavelength of luciferin produced in the presence of the control. In a second aspect of the disclosure, a method for screening a test compound for capability t o modulate one or more members of the hydroxysteroid (17-beta) dehydrogenase (HSD17B) family comprises contacting a first cell expressing an HSD17B family member protein with a test compound and a substrate for the HSD17B family member protein, contacting a second cell expressing the same HSD17B family member protein with a control and a substrate for the HSD17B family member protein, determining the level of substrate depletion by the cells, and identifying the test compound as an inhibitor of the HSD17B family member protein when the level of substrate depletion in the presence of the test compound is lower than the level of substrate depletion in the presence of the control, or identifying the test compound as an activator of the HSD17B family member protein when the level of substrate depletion in the presence of the test compound is higher than the level of substrate depletion in the presence of the control. In a third aspect of the disclosure, a method for screening a test compound for capability t o modulate one or more members of the hydroxysteroid (17-beta) dehydrogenase (HSD17B) family comprises contacting a first cell expressing an HSD17B family member protein with a test compound and a substrate for the HSD17B family member protein, contacting a second cell expressing the same HSD17B family member protein with a control and a substrate for the HSD17B family member protein, determining the level of substrate product produced by the cells, and identifying the test compound as an inhibitor of the HSD17B family member protein when the level of substrate product produced in the presence of the test compound is lower than the level of substrate product produced in the presence of the control, or identifying the test compound as an activator of the HSD17B family member protein when the level of substrate product produced in the presence of the test compound is lower than the level of substrate product produced in the presence of the control. In a fourth aspect of the disclosure, a kit for screening a test compound for capability t o modulate one or more members of the hydroxysteroid (17-beta) dehydrogenase (HSD17B) family comprises an HSD17B family member protein or a cell expressing an HSD17B family member protein, a substrate for the HSD17B family member protein, and instructions for using the HSD17B family member protein or cell expressing the HSD17B family member protein and substrate in a method for screening a test compound for capability t o modulate the HSD17B family member protein.