Patent ID: 8900589
Filing Date: 2014-12-02
Classification: A61K,A61P,C07K

Abstract:
1. An antibody-drug conjugate compound comprising an antibody covalently attached by a linker L and an optional spacer Z to one or more anthracycline derivative drug moieties D, the compound having the formula or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody; D is an anthracycline derivative selected from the structures A and B: where the wavy line indicates the attachment to L; L is a linker selected from —CH —N(R)(C —N(R)—, —N(R) —N(R)(C —N(R)(C —N(R)(CH and the structures: where the wavy lines indicate the attachments to D and Z; and Z is an optional spacer selected from —CH —CH and the structures: R is H, C R Z X —S—, —CH —(CH —(CH —(C —(C X m is 0 or 1; n is 1 to 6; and p is an integer from 1 to 8, wherein Ab is an antibody which binds to one or more tumor-associated antigens or cell-surface receptors selected from (1)-(36): (1) BMPR1B (bone morphogenetic protein receptor-type IB); (2) E16 (LAT1, SLC7A5); (3) STEAP1 (six transmembrane epithelial antigen of prostate); (4) 0772P (CA125, MUC16); (5) MPF (MPF, MSLN, SMR, megakaryocyte potentiating factor, mesothelin); (6) Napi3b (NAPI-3B, NPTIIb, SLC34A2, solute carrier family 34 (sodium phosphate), member 2, type II sodium-dependent phosphate transporter 3b); (7) Sema 5b (FLJ10372, KIAA1445, Mm.42015, SEMA5B, SEMAG, Semaphorin 5b Hlog, sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5B); (8) PSCA hlg (2700050C12Rik, C530008O16Rik, RIKEN cDNA 2700050C12, RIKEN cDNA 2700050C12 gene); (9) ETBR (Endothelin type B receptor); (10) MSG783 (RNF124, hypothetical protein FLJ20315); (11) STEAP2 (HGNC (12) TrpM4 (BR22450, FLJ20041, TRPM4, TRPM4B, transient receptor potential cation channel, subfamily M, member 4); (13) CRIPTO (CR, CR1, CRGF, CRIPTO, TDGF1, teratocarcinoma-derived growth factor); (14) CD21 (CR2 (Complement receptor 2) or C3DR (C3d/Epstein Barr virus receptor) or Hs 73792); (15) CD79b (CD79B, CD79β, IGb (immunoglobulin-associated beta), B29); (16) FcRH2 (IFGP4, IRTA4, SPAP1A (SH2 domain containing phosphatase anchor protein 1a), SPAP1B, SPAP1C); (17) HER2 (ErbB2); (18) NCA (CEACAM6); (19) MDP (DPEP1); (20) IL20Rα (IL20Ra, ZCYTOR7); (21) Brevican (BCAN, BEHAB); (22) EphB2R (DRT, ERK, Hek5, EPHT3, Tyro5); (23) ASLG659 (B7h); (24) PSCA (Prostate stem cell antigen precursor); (25) GEDA (lipoma HMGIC fusion-partner-like protein); (26) BAFF-R (B cell-activating factor receptor, BLyS receptor 3, BR3); (27) CD22 (B-cell receptor CD22-B isoform); (28) CD79a (CD79A, CD79α, immunoglobulin-associated alpha); (29) CXCR5 (Burkitt's lymphoma receptor 1); (30) HLA-DOB (Beta subunit of MHC class II molecule (Ia antigen)); (31) P2X5 (Purinergic receptor P2X ligand-gated ion channel 5); (32) CD72 (B-cell differentiation antigen CD72, Lyb-2); (33) LY64 (Lymphocyte antigen 64 (RP105), type I membrane protein of the leucine rich repeat (LRR) family); (34) FcRH1 (Fc receptor-like protein 1); (35) IRTA2 (Fc receptor-like protein 1, Immunoglobulin superfamily receptor translocation associated 2); and (36) TENB2 (TMEFF2, tomoregulin, TPEF, HPP1, TR, putative transmembrane proteoglycan).