Antibody molecules to tim-3 and uses thereof

Patent metadata

Field	Value
Publication number	US-2020308277-A1
Application number	US-202016841029-A
Country	US
Kind code	A1
Filing date	Apr 6, 2020
Priority date	Jan 31, 2014
Publication date	Oct 1, 2020
Grant date	—

Abstract

Antibody molecules that specifically bind to TIM-3 are disclosed. The anti-TIM-3 antibody molecules can be used to treat, prevent and/or diagnose immune, cancerous, or infectious conditions and/or disorders.

First claim

What is claimed is:

1 . A method of treating a hematological cancer, comprising administering to a subject in need thereof an antibody molecule capable of binding to human TIM-3 in an amount effective to treat the hematological cancer, wherein the antibody molecule comprises:
(a) a heavy chain variable region (VH) comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 10; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a light chain variable region (VL) comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14; (b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 4; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8; (c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 25; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14; (d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 24; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8; (e) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 31; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14; or (f) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 30; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8.

2 . The method of claim 1 , wherein the hematological cancer is a leukemia, a lymphoma, or a myeloma, or a metastatic lesion thereof.

3 . The method of claim 1 , wherein the hematological cancer is a B-cell acute lymphoid leukemia (BALL), a T-cell acute lymphoid leukemia (TALL), an acute myeloid leukemia (AML), an acute lymphoid leukemia (ALL), a chronic myelogenous leukemia (CML), a chronic lymphocytic leukemia (CLL), a B cell prolymphocytic leukemia, a blastic plasmacytoid dendritic cell neoplasm, a Burkitt's lymphoma, a diffuse large B cell lymphoma, a Follicular lymphoma, a hairy cell leukemia, a small cell- or a large cell-follicular lymphoma, a malignant lymphoproliferative condition, a MALT lymphoma, a mantle cell lymphoma, a Marginal zone lymphoma, a multiple myeloma, a myelodysplasia and myelodysplastic syndrome, a non-Hodgkin's lymphoma, a plasmablastic lymphoma, a plasmacytoid dendritic cell neoplasm, a Waldenstrom macroglobulinemia, a preleukemia, or a metastatic lesion thereof.

4 . The method of claim 1 , wherein the antibody molecule is administered in combination with a second therapeutic agent or procedure.

5 . The method of claim 4 , wherein the antibody molecule is administered concurrently with, prior to, or subsequent to the second therapeutic agent or procedure.

6 . The method of claim 4 , wherein the second therapeutic agent or procedure is one or more of a chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a cytokine, a surgical procedure, a radiation procedure, an activator of a costimulatory molecule, an inhibitor of an inhibitory molecule, a vaccine, or a cellular immunotherapy.

7 . The method of claim 1 , wherein the antibody molecule is administered in combination with an agonist of a costimulatory molecule or an inhibitor of an immune checkpoint molecule,
wherein the costimulatory molecule is OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3 or CD83 ligand; or wherein the antibody molecule is administered in combination with an inhibitor of an immune checkpoint molecule, wherein the immune checkpoint molecule is PD-1, PD-L1, PD-L2, CTLA-4, LAG-3, CEACAM-1, CEACAM-5, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 or TGFR.

8 . The method of claim 1 , wherein the antibody molecule is administered in combination with an inhibitor of PD-1.

9 . The method of claim 8 , wherein the inhibitor of PD-1 is an anti-PD-1 antibody molecule or a fusion protein, or is MDX-1106, Merck 3475, AMP-224, or AMP-514.

10 . The method of claim 1 , wherein the antibody molecule is administered in combination with an inhibitor of PD-L1.

11 . The method of claim 1 , wherein the inhibitor of PD-L1 is an anti-PD-L1 antibody molecule or a fusion protein, or is YW243.55.S70, MPDL3280A, MEDI-4736, MSB-0010718C, or MDX-1105.

12 . The method of claim 1 , wherein the antibody molecule is administered in combination with a chemotherapeutic agent.

13 . The method of claim 1 , wherein the chemotherapeutic agent comprises cytarabine, daunorubicin, idarubicin, clofarabine, decitabine, vosaroxin, azacitidine, clofarabine, ribavirin, CPX-351, treosulfan, or elacytarabine.

14 . The method of claim 1 , wherein the antibody molecule is administered in combination with a chemotherapeutic, a tyrosine kinase inhibitor, an immunotoxin, a DT388IL3 fusion protein, interferon alfa, a steroid, an apoptotic agent, an immunotherapy, a CD52 targeting agent, an HSP90 inhibitor, an mTOR inhibitor, a SMO antagonist, a ribonucleotide reductase inhibitor, a JAK-2 inhibitor, hydroxychloroquine, a retinoid, a cyclin-dependent kinase inhibitor, an HDAC inhibitor, a PARP inhibitor, an MDM2 antagonist, an aurora B kinase inhibitor, a radioimmunotherapy, a hedgehog inhibitor, a STAT3 inhibitor, KB004, a cancer vaccine, a bone marrow transplantation, a stem cell transplantation, a radiation therapy, a SRC inhibitor, a polo-like kinase inhibitor, cenersen, a CD45 targeting agent, a cyclin-dependent kinase inhibitor, LY573636-sodium, ZRx-101, MLN4924, lenalidomide, histamine dihydrochloride, or a combination thereof.

15 . The method of claim 1 , wherein the subject has, or is identified as having, a hematological cancer that:
(a) expresses TIM-3; (b) is positive for one, two, or all of PD-L1, CD8, or IFN-γ; or (c) is tumor infiltrating lymphocyte (TIL) positive.

16 . The method of claim 1 , wherein the antibody molecule is administered:
(a) at a dose of about 0.1 to 30 mg/kg; (b) at a dose of about 1 to 5 mg/kg; (c) once a week to once every 2, 3, or 4 weeks; or (d) once a week to once every 2, 3, or 4 weeks.

17 . The method of claim 1 , wherein said antibody molecule is a humanized antibody molecule, and/or comprises an antigen binding fragment of an antibody, a half antibody or antigen binding fragment of a half antibody, or a Fab, F(ab′)2, Fv, or a single chain Fv fragment (scFv).

18 . The method of claim 1 , wherein said antibody molecule comprises:
(a) a VH comprising the amino acid sequence of SEQ ID NO: 1, 16, 26, 32, 36, 44, 48, 52, 60, 68, 72, 76, 80, 84, 92, or 100, or an amino acid sequence at least 85% identical to any of the amino acid se

Assignees

• Novartis Ag
• Dana Farber Cancer Inst Inc
• Childrens Medical Ct Corp

Inventors

• Sabatos-Peyton Catherine Anne
• Brannetti Barbara
• Harris Alan S
• Huber Thomas
• Pietzonka Thomas
• Mataraza Jennifer Marie
• Blattler Walter A
• Hicklin Daniel J
• Vasquez Maximiliano
• Dekruyff Rosemarie H
• Umetsu Dale T
• Freeman Gordon James
• Hu Tiancen
• Taraszka John A
• Xu Fangmin

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• G01N2333/70596

  Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title