Antibody molecules to TIM-3 and uses thereof

Patent metadata

Field	Value
Publication number	US-9605070-B2
Application number	US-201514610837-A
Country	US
Kind code	B2
Filing date	Jan 30, 2015
Priority date	Jan 31, 2014
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

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 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 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,
wherein the cancer is selected from the group consisting of a lung cancer, a melanoma, a renal cancer, a breast cancer, a colorectal cancer, a hepatocarcinoma, a prostate cancer, or a metastatic lesion thereof.

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

3. The method of claim 2 , wherein the antibody molecule is administered in combination with an agonist of a costimulatory 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.

4. The method of claim 2 , 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.

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

6. The method of claim 5 , wherein the inhibitor of PD-1 is an anti-PD-1 antibody molecule or a fusion protein.

7. The method of claim 5 , wherein the inhibitor of PD-1 is MDX-1106, Merck 3475, CT-011, AMP-224, or AMP-514.

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

9. The method of claim 8 , wherein the inhibitor of PD-L1 is an anti-PD-L1 antibody molecule or a fusion protein.

10. The method of claim 8 , wherein the inhibitor of PD-L1 is YW243.55.S70, MPDL3280A, MEDI-4736, MSB-0010718C, or MDX-1105.

11. The method of claim 1 , wherein the antibody molecule is administered in combination with an inhibitor of LAG-3.

12. The method of claim 11 , wherein the inhibitor of LAG-3 is an anti-LAG-3 antibody molecule or a fusion protein.

13. The method of claim 1 , wherein the antibody molecule is administered in combination with an agonist of GITR.

14. The method of claim 13 , wherein the agonist of GITR is an anti-GITR antibody molecule or a fusion protein.

15. The method of claim 2 , 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.

16. The method of claim 1 , wherein the lung cancer is a non-small cell lung cancer (NSCLC), a lung adenocarcinoma, a squamous cell lung carcinoma, or a small cell lung cancer.

17. The method of claim 1 , wherein the lung cancer is a non-small cell lung cancer.

18. The method of claim 1 , wherein the melanoma is an advanced melanoma, an unresectable melanoma, a metastatic melanoma, a melanoma with a BRAF mutation, a melanoma with an NRAS mutation, a cutaneous melanoma, or an intraocular melanoma.

19. The method of claim 1 , wherein the renal cancer is a renal cell carcinoma (RCC), a metastatic renal cell carcinoma, a clear cell renal cell carcinoma (CCRCC), a kidney clear cell carcinoma, or a kidney papillary cell carcinoma.

20. The method of claim 1 , wherein the renal cancer is a renal cell carcinoma or a metastatic renal cell carcinoma.

21. The method of claim 1 , wherein the antibody molecule is administered in combination with a chemotherapy to treat a lung cancer.

22. The method of claim 21 , wherein the chemotherapy is a platinum doublet therapy.

23. The method of claim 1 , wherein the antibody molecule is administered in combination with an indoleamine-pyrrole 2,3-dioxygenase (IDO) inhibitor to treat a lung cancer.

24. The method of claim 23 , wherein the IDO inhibitor is INCB24360.

25. The method of claim 1 , wherein the antibody molecule is administered in combination with an inhibitor of CTLA-4 to treat a lung cancer or a melanoma.

26. The method of claim 25 , wherein the inhibitor of CTLA-4 is an anti-CTLA-4 antibody or a soluble ligand of CTLA-4.

27. The method of claim 26 , wherein the anti-CTLA-4 antibody is ipilimumab.

28. The method of claim 25 , wherein the antibody molecule is administered further in combination with a BRAF inhibitor.

29. The method of claim 28 , wherein the BRAF inhibitor is vemurafenib or dabrafenib.

30. The method of claim 1 , wherein the antibody molecule is administered in combination with a MEK inhibitor to treat a lung cancer, a melanoma, or a renal cancer.

31. The method of claim 1 , wherein the antibody molecule is administered in combination with a cancer vaccine.

32. The method of claim 31 , wherein the cancer vaccine is a dendritic cell renal carcinoma (DC-RCC) vaccine.

33. The method of claim 1 , wherein the antibody molecule is administered in combination with one or more of: an immune-based therapy, a targeting agent, a VEGF tyrosine kinase inhibitor, an RNAi inhibitor, or an inhibitor of a downstream mediator of VEGF signal

Assignees

• Novartis Ag
• Dana Farber Cancer Inst Inc
• Children'S Medical Center 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

• A61P35/04

  specific for metastasis · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title