ESSENTIALACTIVATING DOMAIN:CDX W O 18/ 200 496 Al 5'LTR scFv CDS?, KIR CAR VECTOR CONSTRUCT TARGET BINDING DOMAIN: ANTIBODY DERIVED )scFv) HINGE RA.NSMEMBRANE DOMAIN COSTIMULATORY DOMAIN:CD28 CAR-ENGINEERED T CELL FIG. 1A (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 01 November 2018 (01.11.2018) WIPO I PCT ~ill IIIIIIIIIImillIVIIIIIIIHo o olo um Immo oimIE (10) International Publication Number WO 2018/200496 Al (51) International Patent Classification: A61P 35/02 (2006.01) C07K 16/28 (2006.01) (21) International Application Number: PCT/US2018/029107 (22) International Filing Date: 24 April 2018 (24.04.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/489,258 24 April 2017 (24.04.2017) US (71) Applicant: KITE PHARMA, INC. [US/US]; 2225 Col- orado Avenue, Santa Monica, CA 90404 (US). (72) Inventors: WILTZIUS, Jed, J.W.; c/o Kite Pharma, Inc., 2225 Colorado Avenue, Santa Monica, CA 90404 (US). SIEVERS, Stuart, A.; c/o Kite Pharma, Inc., 2225 Col- orado Avenue, Santa Monica, CA 90404 (US). (74) Agent: BARBIC, Andrej et al.; Proskauer Rose LLP, One International Place, Boston, MA 02110 (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, 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). Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) (54) Title: HUMANIZED ANTIGEN-BINDING DOMAINS AGAINST CD19 AND METHODS OF USE (57) : The invention provides a humanized anti-CD 19 antibody or antigen binding fragment thereof comprising a light chain variable (VL) region and a heavy chain variable (VH) region in which the humanized VL and VL regions are derived from the mouse anti-CD 19 clone FMC63 antibody; the humanized VL and/or humanized VH region comprise one or more amino acid substitutions in the framework region. The humanized anti-CD 19 antibody or antigen binding fragment may be part of a single chain variable fragment (scFv), a chimeric antigen receptor (CAR) or a T cell receptor (TCR). Other aspects of the invention relate to cells compris- ing the CAR or the TCR and their use in a T cell therapy.
HUMANIZED ANTIGEN-BINDING DOMAINS AGAINST CD19 AND METHODS OF USE