PHARMACEUTICAL COMPOSITIONS AND METHODS USEFUL FOR MODULATING ANGIOGENESIS, INHIBITING METASTASIS AND TUMOR FIBROSIS, AND ASSESSING THE MALIGNANCY OF COLON CANCER TUMORS

• US 20100119515A1
• Filed: 09/30/2009
• Published: 05/13/2010
• Est. Priority Date: 11/27/2002
• Status: Active Grant

• Current Assignee: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD.
• Original Assignee: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD.
• Inventors: Gengrinovitch, Stela, Akiri, Gal, Vadasz, Zahava, Neufeld, Gera
• Granted Patent: US 8,168,180 B2
• Time in Patent Office: Days
• US Class Current: 424/139.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 9/0022 with oxygen as acceptor (1.4.3)
• CPC Class Codes: C12Q 1/26 involving oxidoreductase
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Y 104/03013 Protein-lysine 6-oxidase (1.4.3.13), i.e. lysyl-oxidase
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57419 of colon

Abstract

Methods and compositions suitable for modulating angiogenesis in a mammalian tissue are provided. Further provided are methods suitable for inhibiting metastasis and fibrosis in a mammalian tissue and for assessing the malignancy of colon cancer tumors.

Claims

1-51. -51. (canceled)

52. A method of modulating angiogenesis in a subject, the method comprising modifying the activity of lysyl oxidase-related protein 1 (LOR-1) in the subject.

53. The method of claim 52, wherein the modulation is inhibition of angiogenesis, and further wherein the method comprises administering to the subject a molecule that inhibits the activity of a polypeptide having at least 75% homology to SEQ ID NO:

2.

54. The method of claim 53, wherein the polypeptide having at least 75% homology to SEQ ID NO:

2 is LOR-1.

55. The method of claim 54, wherein the LOR-1 polypeptide has the amino acid sequence set forth in SEQ ID NO:

2.

56. The method of claim 52, wherein the angiogenesis is involved in tumor growth.

57. The method of claim 52, wherein the angiogenesis is involved in tumor invasiveness.

58. The method of claim 52, wherein the angiogenesis is involved in tumor metastasis.

59. The method of claim 53, wherein said molecule is a polypeptide that inhibits LOR-1 activity.

60. The method of claim 59, wherein said polypeptide that inhibits LOR-1 activity is an antibody or an antibody fragment that binds to said polypeptide having at least 75% homology to SEQ ID NO:

2.

61. The method of claim 60, wherein said antibody or said antibody fragment is directed against a portion of the polypeptide set forth in SEQ ID NO:

2.

62. The method of claim 53, wherein said molecule is a nucleic acid encoding a polypeptide that inhibits LOR-1 activity.

63. The method of claim 62, wherein said polypeptide that inhibits LOR-1 activity is an antibody or an antibody fragment that binds to said polypeptide having at least 75% homology to SEQ ID NO:

2.

64. The method of claim 63, wherein said antibody or said antibody fragment is directed against a portion of the polypeptide set forth in SEQ ID NO:

2.

65. The method of claim 53, wherein said molecule is a polynucleotide that down-regulates expression of LOR-1.

66. The method of claim 65, wherein the nucleotide sequence of the polynucleotide is at least partially complementary to the nucleotide sequence set forth in SEQ ID NO:

1 or its complement.

67. The method of claim 52, wherein the modulation is promoting angiogenesis, and further wherein the method comprises administering to the subject a polypeptide having at least 75% homology to SEQ ID NO:

2.

68. The method of claim 67, wherein said polypeptide having at least 75% homology to SEQ ID NO:

2 is LOR-1

69. The method of claim 68, wherein said polypeptide having at least 75% homology to SEQ ID NO:

2 has the amino acid sequence set forth in SEQ ID NO;

2.

70. The method of claim 67, wherein administering to the subject comprises administering a nucleic acid encoding a polypeptide having at least 75% homology to SEQ ID NO:

2.

71. The method of claim 70, wherein said polypeptide having at least 75% homology to SEQ ID NO:

2 is LOR-1.

72. The method of claim 71, wherein said polypeptide having at least 75% homology to SEQ ID NO:

2 has the amino acid sequence set forth in SEQ ID NO;

2.

73. The method of claim 53, wherein the molecule is administered locally.

74. The method of claim 67, wherein the polypeptide is administered locally.

75. The method of claim 70, wherein the nucleic acid is administered locally.