Pharmaceutical compositions and methods useful for modulating angiogenesis, inhibiting metastasis and tumor fibrosis, and assessing the malignancy of colon cancer tumors

• US 8,815,823 B2
• Filed: 03/09/2012
• Issued: 08/26/2014
• Est. Priority Date: 11/27/2002
• Status: Expired due to Fees

• Current Assignee: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD. (Technion-Israel Institute Of Technology)
• Original Assignee: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD. (Technion-Israel Institute Of Technology)
• Inventors: Neufeld, Gera, Akiri, Gal, Vadasz, Zahava, Gengrinovitch, Stela
• Primary Examiner(s): SCHNIZER, RICHARD A
• Application Number:
  US13/416,976
• Publication Number:
  US 20120165398A1
• Time in Patent Office: 900 Days
• Field of Search: None
• US Class Current: 514/44.A
• 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. A method of inhibiting angiogenesis in a subject, comprising:

administering to the subject a polynucleotide of at least 15 bases that specifically hybridizes under physiological conditions to a nucleic acid having the nucleotide sequence of SEQ ID NO;

1,

thereby inhibiting angiogenesis in the subject.

2. The method of claim 1, wherein the angiogenesis in the subject is involved in tumor growth, invasiveness, or metastasis.

3. The method of claim 1, wherein the polynucleotide is administered locally.

4. The method of claim 1, wherein the polynucleotide is administered systemically.

5. The method of claim 1, wherein the subject has a breast tumor.

6. The method of claim 1, wherein the subject has a metastasis of a breast tumor.

7. The method of claim 1, wherein the subject has a colon tumor.

8. The method of claim 1, wherein the subject has a metastasis of a colon tumor.

9. The method of claim 1, wherein the polynucleotide comprises between 15 and 20 bases.

10. The method of claim 1, wherein the polynucleotide comprises between 15 and 40 bases.

11. A method of inhibiting angiogenesis in a subject, comprising:

administering to the subject an antisense polynucleotide of at least 15 bases capable of hybridizing under physiological conditions to an mRNA encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO;

2, thereby inhibiting angiogenesis in the subject.

12. The method of claim 11, wherein the polynucleotide is complementary to a nucleic acid having the nucleotide sequence of SEQ ID NO:

1.

13. The method of claim 11, wherein the subject has a breast tumor.

14. The method of claim 11, wherein the subject has a colon tumor.

15. A method of inhibiting angiogenesis in a subject, comprising:

administering to the subject a polynucleotide of at least 15 bases that is complementary to a nucleic acid having the nucleotide sequence of SEQ ID NO;

1,

thereby inhibiting angiogenesis in the subject.

16. The method of claim 15, wherein the subject has a breast tumor.

17. The method of claim 15, wherein the subject has a colon tumor.

18. The method of claim 15, wherein the polynucleotide comprises between 15 and 20 bases.

19. The method of claim 15, wherein the polynucleotide comprises between 15 and 40 bases.