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WO 2019/224717 A2 28 November 2019 (28.11.2019) W P O I PCT

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WO 2019/224717 A2 28 November 2019 (28.11.2019) W P O I PCT (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 2019/224717 A2 28 November 2019 (28.11.2019) W P O I PCT (51) International Patent Classification: SEAY, Jennifer; 1400 McKean Road, SpringHouse, Penn¬ C07K 16/28 (2006.01) sylvania 19477 (US). (21) International Application Number: (74) Agent: SHIRTZ, Joseph F. et al.; Johnson & Johnson, PCT/IB20 19/054 188 One Johnson & Johnson Plaza, New Brunswick, New Jer¬ sey 08933 (US). (22) International Filing Date: 2 1 May 2019 (21.05.2019) (81) Designated States (unless otherwise indicated, for every kind of national protection av ailable) . AE, AG, AL, AM, (25) Filing Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (26) Publication Language: English 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, (30) Priority Data: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/676,081 24 May 2018 (24.05.2018) US KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (71) Applicant: JANSSEN BIOTECH, INC. [US/US]; MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 800/850 Ridgeview Drive, Horsham, Pennsylvania 19044 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (US). 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. (72) Inventors: GAUDET, Francois; 1400 McKean Road, Spring House, Pennsylvania 19477 (US). GILES-KO- (84) Designated States (unless otherwise indicated, for every MAR, Jill; 31 Blakely Road, Downington, Pennsylvania kind of regional protection available) . ARIPO (BW, GH, 19335 (US). HEIDRICH, Bradley; 1400 McKean Road, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, SpringHouse, Pennsylvania 19477 (US). HUANG, Chichi; UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 22 Dobs In, Malvern, Pennsylvania 19355 (US). KANE, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Colleen; 1400 McKean Road, Spring House, Pennsylva¬ EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, nia 19477 (US). MCDAID, Ronan; 19 Ludlow Road, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Suite 202, Westport, Connecticut 06880 (US). NEMETH- (54) Title: ANTI-CD 3 ANTIBODIES AND USES THEREOF (57) Abstract: The present invention relates to antibodies that specifically bind CD3. The present invention relates to antibodies that specifically bind PSMA. The present in¬ vention relates to antibodies that specifically bind CD3 and PSMA. The present inven¬ tion relates to antibodies that specifically bind IL1RAP. The present invention relates to antibodies that specifically bind CD33. The present invention relates to antibodies that specifically bind CD3 and ILIRAP. The present invention relates to antibodies that specifically bind CD3 and CD33. The present invention relates to antibodies that specifically bind TMEFF2. The present invention relates to antibodies that specifically bind CD3 and TMEFF2. The present invention relates to fragments of the antibodies, polynucleotides encoding the antibodies or fragments thereof, and methods of making and using the same. [Continued on next page] W O 2019/224717 A2 TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) Published: without international search report and to be republished upon receipt of that report (Rule 48.2(g)) with sequence listing part of description (Rule 5.2(a)) in black and white; the international application as filed contained color or greyscale and is availablefor download from PATENTSCOPE ANTI-CD3 ANTIBODIES AND USES THEREOF SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 3, 2019, is named JBI5l35WOPCTl_Sequence_listing.txt and is 588 KB in size. TECHNICAL FIELD The disclosure provided herein relates to anti-cluster of differentiation 3 (CD3)- antibodies, and antigen-binding fragments thereof, capable of specifically binding to human and non-human CD3, and in particular to anti-CD3 antibodies and antigen-binding fragments that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey); prostate specific membrane antigen (PSMA)-antibodies, and antigen-binding fragments thereof, capable of specifically binding to human and non-human PSMA; IL1RAP antibodies, and antigen binding fragments thereof, capable of specifically binding to human and non-human IL1RAP; CD33 antibodies, and antigen-binding fragments thereof, capable of specifically binding to human and non-human CD33; and bispecific antibodies that are capable of specifically binding CD3; PSMA; IL1RAP; CD33; CD3 and PSMA; CD3 and IL1RAP; or CD3 and CD33. The disclosure also pertains to uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions. BACKGROUND Bispecific antibodies and antibody fragments have been explored as a means to recruit cytolytic T cells to kill tumor cells. However, the clinical use of many T cell-recruiting bispecific antibodies has been limited by challenges including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing issues. There thus exists a considerable need for bispecific antibodies that recruit cytolytic T cells to kill tumor cells that exhibit reduced toxicity and favorable manufacturing profiles. The human CD3 T cell antigen receptor protein complex is composed of six distinct chains: a CD3y chain (SwissProt P09693), a CD35 chain (SwissProt P04234), two CD3ε chains (SwissProt P07766), and one 3 chain homodimer (SwissProt P20963) ( : : ), which is associated with the T cell receptor a and chain. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. CD3 is required for immune response. SUMMARY Provided herein are isolated recombinant anti-CD3 antibodies, or antigen-binding fragments thereof, comprising: a heavy chain comprising a heavy chain complementarity determining region (HCDR) 1 comprising SEQ ID NO: 662; a HCDR2 comprising SEQ ID NO: 663; and a HCDR3 comprising SEQ ID NO: 664 and a light chain comprising a light chain complementarity determining region (LCDR) 1 comprising SEQ ID NO: 671, a LCDR2 comprising SEQ ID NO: 673, and a LCDR3 comprising SEQ ID NO: 690; a heavy chain variable region comprising SEQ ID NO: 652 and a light chain variable region comprising SEQ ID NO: 661; a heavy chain comprising SEQ ID NO: 640 and a light chain comprising SEQ ID NO: 676; or comprising: a heavy chain comprising a HCDR1 comprising SEQ ID NO: 662; a HCDR2 comprising SEQ ID NO: 663; and a HCDR3 comprising SEQ ID NO: 664 and a light chain comprising a LCDR1 comprising SEQ ID NO: 773, a LCDR2 comprising SEQ ID NO: 673, and a LCDR3 comprising SEQ ID NO: 690; a heavy chain variable region comprising SEQ ID NO: 657 and a light chain variable region comprising SEQ ID NO: 678; or a heavy chain comprising SEQ ID NO: 675 and a light chain comprising SEQ ID NO: 678. Also provided are isolated recombinant anti-CD3 antibodies or antigen-binding fragments thereof, that specifically bind Macacafascicularis or human CD3d, or CD3e, or CD3e and CD3d with a binding affinity of about 300 nM or less. In some embodiments, the isolated recombinant anti-CD3 antibodies or antigen-binding fragments thereof have one, two, three, or four, of the following properties: • bind human and Macaca fascicularis CD3+ T lymphocytes with a calculated EC50 of 20 nM or less and bind Macaca fascicularis CD3-expressing HEK cells with a calculated EC50 of 40 nM or less, wherein the difference in calculated EC50 between binding CD3+ T lymphocytes and binding Macaca fascicularis CD3- expressing HEK cells is less than 5-fold, and wherein the calculated EC50 is measured in a whole cell binding assay at 0 °C using flow cytometry; bind recombinant CD3d from human (SEQ ID NO:69l), or bind recombinant CD3e from human (SEQ ID NO: 636), or recombinant CD3d from Macaca fascicularis (SEQ ID NO: 692), with an equilibrium dissociation constant (KD) of 12 nM or less, wherein the KD is measured using Proteon surface plasmon resonance assay ProteOn XPR36 system at +25°C; bind residues 1-6 of CD3e as determined by X-ray crystallography; or activate T cells or induces CD69 expression to a similar degree as cOKT3 or SP34- 2 as determined by fluorescence-activated cell sorting assay. In some embodiments, the antibodies or antigen-binding fragments thereof described herein comprise the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 of SEQ ID NOs:662, 663, 664, 671, 673, and 690, respectively; a VH and a VL of SEQ ID NOs:652 and 661, respectively; or a HC and a LC of SEQ ID NOs:640 and 676, respectively. In some embodiments, the antibodes or antigen-binding fragments thereof described herein comprise the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 of SEQ ID NOs:662, 663, 664, 773, 673, and 690, respectively; a VH and a VL of SEQ ID NOs:657 and 678, respectively or a HC and a LC of SEQ ID NOs:675 and 677, respectively.
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