Patent SG-11201903331Q-A (SG)
Title: Restimulation of cryopreserved tumor infiltrating lymphocytes
Inventor: FRANK IAN
IPC: C12N5/0783
Filed: 2017-10-26
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization 1#11101111 01110101011111 01111101 0 011111111111 010 1110 11111 011111110 1111 0111111 International Bureau (10) International Publication Number (43) International Publication Date ......0\"\"1 WO 2018/081473 Al 03 May 2018 (03.05.2018) WIP0 I PCT (51) International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, C12N 5/0783 (2010.01) A61K 35/17 (2015.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US2017/058610 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. (22) International Filing Date: (84) Designated States (unless otherwise indicated, for every 26 October 2017 (26.10.2017) kind of regional protection available): ARIPO (BW, GH, (25) Filing Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (30) Priority Data: EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 62/413,387 26 October 2016 (26.10.2016) US MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, 62/413,283 26 October 2016 (26.10.2016) US TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 62/415,452 31 October 2016 (31.10.2016) US KM, ML, MR, NE, SN, TD, TG). (71) Applicant: IOVANCE BIOTHERAPEUTICS, INC. Declarations under Rule 4.17: [US/US]; 999 Skyway Road, Suite 150, San Carlos, CA - as to applicant's entitlement to apply for and be granted a 94070 (US). patent (Rule 4.1700) (72) Inventors: FRANK, Ian; 8302 Old Town Drive, Tampa, - as to the applicant's entitlement to claim the priority of the _ FL 33647 (US). LOTZE, Michael, T.; 5134 Westminster earlier application (Rule 4.17(iii)) Place, Pittsburgh, PA 15232 (US). Published: - (74) Agent: MACDOUGALL, Christina, A. et al.; Morgan, Lewis & Bockius LLP, One Market, Spear Tower, San Fran- - with international search report (Art. 21(3)) - before the expiration of the time limit for amending the _ = cisco, CA 94105 (US). claims and to be republished in the event of receipt of = Designated States (unless otherwise indicated, for every amendments (Rule 48.2(h)) = (81) 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, = Title: RESTIMULATION OF CRYOPRESERVED TUMOR INFILTRATING LYMPHOCYTES = (54) = Figure 1 = = = = Table 1. = Fresh Product Cryopreserved Product )8 147 3 Al 11111111111 Tumor Type post-Harvest post-Thaw post-restimulation Malignant Melanoma OxPhos (pmol/min) (M1053T) Basal respiration 17.5 ± 4.4 9.5 ± 4.9 22.5 ± 2.5 REP SRC 19.3 ± 9.0 27.5± 12.1 16.8 ± 2.6 SRC (% of basal) 210.6 ± 51.4 389.8 ± 127.4 174.7 ± 11.3 Glycolysis (mpH/min) Basal glycolysis 31.1 ± 4.4 22.5± 1.2 103.1 ± 5.4 Glycolytic Reserve 26.4± 5.5 20.7 ± 2.2 15.9 ± 7.7 Glycolytic Res (% of basal) 185.1 ± 17.6 192.0 ± 9.9 115.5 ± 7.4 .. .... 7 .... GC Il 0 el (57) : The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and in- creased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious 0 infusion after re- stimulation.