Patent SG-11201807286W-A (SG)
Title: Methods and compositions for transducing lymphocytes and regulated expansion thereof
Inventor: FROST GREGORY IAN
IPC: C12N15/10
Filed: 2017-03-19
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -, Organization MD 1111101110101011111 HO 11111 01110111101111010101111111111111011 International Bureau 0.. .... .. (10) International Publication Number ...... ... (43) International Publication Date WO 2017/165245 A2 28 September 2017 (28.09.2017) WIP0 I PCT (51) International Patent Classification: (US). KUNDU, Anirban; 229 Boltin Ave. Apt-4, Grand C12N 15/10 (2006.01) CO7K 14/725 (2006.01) Cayman, KY1 (KY). C12N 15/867 (2006.01) CO7K 14/705 (2006.01) C12N 5/0783 (2010.01) C07K 14/715 (2006.01) (74) Agent: VACCHIANO, Emanuel; 8110 Woodside Lane, C12N 5/10 (2006.01) A61K 48/00 (2006.01) Burr Ridge, Illinois 60527 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2017/023112 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filing Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, 19 March 2017 (19.03.2017) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (25) Filing Language: English KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, (26) Publication Language: English MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (30) Priority Data: RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, 62/390,093 19 March 2016 (19.03.2016) US TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, 62/360,041 8 July 2016 (08.07.2016) US ZA, ZM, ZW. 62/467,039 3 March 2017 (03.03.2017) US (84) Designated States (unless otherwise indicated, for every (71) Applicants: Fl ONCOLOGY, INC. [US/US]; 625 N. Fla- kind of regional protection available): ARIPO (BW, GH, gler Dr., Suite 625, West Palm Beach, Florida 33401 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, Fl ONCOLOGY, SEZC; BritCay House, 236 Eastern TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, Avenue, Grand Cayman, KY1 (KY). TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, Inventors: FROST, Gregory Ian; 505 S Flagler Drive, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Suite 900, West Palm Beach, Florida 33401 (US). LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, ONUFFER, James Joseph; 1032 Fountain Street, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Alameda, California 94501 (US). GUIBINGA, Ghiabe GW, KM, ML, MR, NE, SN, TD, TG). (72) _ H.; 1613 Fort Stockton Drive, San Diego, California 92103 [Continued on next page] = Title: METHODS AND COMPOSITIONS FOR TRANSDUCING LYMPHOCYTES AND REGULATED EXPANSION = (54) — THEREOF = = 7 .. ..,-.-.. .., .-.,, F I G . 2 250 300 4.. '`',. • tv.. 200 if - = ' • *-,..,, 350 ‘ , 14 = . ' 1 1r .\" - •:., ‘ , , C = • ft• 10 I li ft - 1 ; 20 1S .7/041_ .;, -„; 1 -- -,-.330 = 340 \" - 1, 44,14.0•A •1 . ••., / ; 0' • 1 -_,- • t ti , ! ---41 1 . ,,, , , , \ - el ' In ./ • . i c ( t3 , i 7r 200 N \" ,k-1.. * 11,„ 360 ir) , A 370 ,tD 1-1 ---- (57) : The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adopt- 1-1 ive cellular therapy that include transducing T cells and/or NK cells without prior ex vivo stimulation. The methods typically include C engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for ex - N ample a microenvironment restricted CAR. Additional elements of such engineered signaling polypeptides are provided herein, as 0 as wellvectors, such as retroviral vectors, packaging cell lines and methods of making the same. Furthermore, recombinant retrovir - ,.1 uses and methods of making the same are provided. Numerous controls are provided, including ribos witches that are controlled, for example in vivo, by nucleoside analogues. WO 2017/165245 A2 11111101110110101011E10130HEIMMOMEEDIS • I \"\"\"°\"\"`' — with sequence listing part of description (Rule 5.2(a)) — without international search report and to be republished upon receipt of that report (Rule 48.2(g))