Compositions and Methods for Diagnosing and Treating Cancer

• US 20100316637A1
• Filed: 05/18/2010
• Published: 12/16/2010
• Est. Priority Date: 09/29/2006
• Status: Active Grant

• Current Assignee: Mereo Biopharma 5 Incorporated
• Original Assignee: OncoMed Pharmaceuticals, Incorporated (Mereo BioPharma Group Plc)
• Inventors: GURNEY, AUSTIN, HOEY, TIM, AXELROD, FUMIKO, SATYAL, SANJEEV
• Granted Patent: US 9,376,497 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3015 Breast
• CPC Class Codes: C07K 16/3023 Lung
• CPC Class Codes: C07K 16/303 Liver or Pancreas
• CPC Class Codes: C07K 16/3046 Stomach, Intestines
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

An isolated antibody that specifically binds to an extracellular domain of human DLL4 and affects growth of a tumor comprising cancer stem cells is described. Also described is a method of treating cancer comprising administering a therapeutically effective amount of an anti-DLL4 antibody.

Claims

1-64. -64. (canceled)

65. A monoclonal antibody that binds an N-terminal fragment of human DLL4 (SEQ ID NO:

25) truncated at amino acid 217.

66. The monoclonal antibody of claim 65, which binds an epitope comprising amino acids within the human DLL4 DSL domain (SEQ ID NO:

26).

67. The monoclonal antibody of claim 65, which binds an epitope comprising amino acids 66-73 of SEQ ID NO:

27 (QAVVSPGP).

68. The monoclonal antibody of claim 65, which binds an epitope comprising amino acids 139-146 of SEQ ID NO:

27 (LISKIAIQ).

69. The monoclonal antibody of claim 65, which binds an epitope comprising amino acids 66-73 of SEQ ID NO:

27 (QAVVSPGP) and amino acids 139-146 of SEQ ID NO;

27 (LISKIAIQ).

70. The monoclonal antibody of claim 65, which is a humanized antibody.

71. The monoclonal antibody of claim 65, which is a human antibody.

72. The monoclonal antibody of claim 65, which is a bispecific antibody.

73. The antibody of claim 65, which is an IgG1 antibody.

74. The antibody of claim 65, which is an IgG2 antibody.

75. The antibody of claim 65, which does not crossreact with human DLL1 or human DLL3.

76. The antibody of claim 65, which does not crossreact with mouse DLL4.

77. The antibody of claim 65, which inhibits tumor growth.

78. The antibody of claim 77, wherein the tumor is colon tumor.

79. The antibody of claim 65, which reduces cancer stem cell frequency in a solid tumor.

80. The antibody of claim 65, which has a K_D of about 0.1 μ

M or less.

82. A pharmaceutical composition comprising the antibody of claim 65 and a pharmaceutically acceptable carrier.

81. A humanized antibody that competes for specific binding to human DLL4 with an antibody encoded by a plasmid deposited with ATCC, having deposit no. PTA-8427 or PTA-8425.

83. A pharmaceutical composition comprising the antibody of claim 81 and a pharmaceutically acceptable carrier.