Anti-angiogenic methods and compositions

• US 7,732,196 B2
• Filed: 12/06/2007
• Issued: 06/08/2010
• Est. Priority Date: 02/28/2005
• Status: Active Grant

• Current Assignee: Sangamo Biosciences, Inc.
• Original Assignee: Sangamo Biosciences, Inc.
• Inventors: Rebar, Edward J., Zhang, H. Steve, Gregory, Philip D.
• Primary Examiner(s): WEHBE, ANNE MARIE SABRINA
• Application Number:
  US11/999,549
• Publication Number:
  US 20080187523A1
• Time in Patent Office: 915 Days
• Field of Search: 435/320.1, 536/23.5
• US Class Current: 435/320.1
• 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 27/02 Ophthalmic agents
• 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 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 14/811 Serine protease (E.C. 3.4.21) inhibitors
• CPC Class Codes: C07K 2319/71 containing domain for transcriptional activaation, e.g. VP16
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus
• CPC Class Codes: C12N 2799/025 where the vector is derived from a parvovirus
• CPC Class Codes: C12N 2799/028 where the vector is derived from a herpesvirus

Abstract

Disclosed herein are methods and compositions for treatment of conditions requiring inhibition of angiogenesis. Such conditions include those characterized by neovascularization, such as retinopathies, macular degeneration and various malignancies.

Claims

1. A polynucleotide encoding two engineered zinc finger proteins, wherein the first zinc finger protein comprises six zinc fingers and the amino acid sequence of the recognition region of each of the zinc fingers is as follows:

2. The polynucleotide of claim 1, further comprising an internal ribosome entry site (IRES) disposed between the sequences encoding the first and second zinc finger proteins.

3. The polynucleotide of claim 1, further comprising a sequence encoding a 2A peptide disposed between the sequences encoding the first and second zinc finger proteins.

4. A polynucleotide encoding two engineered zinc finger proteins, wherein the first zinc finger protein comprises six zinc fingers and the amino acid sequence of the recognition region of each of the zinc fingers is as follows:

5. The polynucleotide of claim 4, further comprising an internal ribosome entry site (IRES) disposed between the sequences encoding the first and second zinc finger proteins.

6. The polynucleotide of claim 4, further comprising a sequence encoding a 2A peptide disposed between the sequences encoding the first and second zinc finger proteins.

7. The polynucleotide of claim 4, wherein sequences encoding the second zinc finger protein are operably linked to a tumor-specific promoter.

8. The polynucleotide of claim 4, wherein sequences encoding the first and second zinc finger proteins are operably linked to a tumor-specific promoter.

9. The polynucleotide of claim 4, wherein sequences encoding the first zinc finger protein are operably linked to a hypoxia-specific promoter.

10. The polynucleotide of claim 4, wherein sequences encoding the second zinc finger protein are operably linked to a hypoxia-specific promoter.

11. The polynucleotide of claim 4, wherein sequences encoding the first zinc finger protein are operably linked to a tissue-specific promoter.

12. The polynucleotide of claim 4, wherein sequences encoding the second zinc finger protein are operably linked to a tissue-specific promoter.

13. The polynucleotide of claim 4, wherein sequences encoding the first zinc finger protein are operably linked to a tumor-specific promoter.

14. The polynucleotide of claim 4, wherein the polynucleotide encodes first and second fusion proteins, the first fusion protein comprising the first zinc finger protein and an activation domain, and the second fusion protein comprising the second zinc finger protein and an activation domain, and further wherein the polynucleotide comprises a promoter sequence operably linked to the sequence encoding the first fusion protein.

15. The polynucleotide of claim 14, wherein sequences encoding the first zinc finger protein are operably linked to a tumor-specific promoter.

16. The polynucleotide of claim 15, wherein the tumor specific promoter is selected from the group consisting of the E2F promoter, the survivin promoter, the human telomerase reverse transcriptase (hTERT) promoter, the COX-2 promoter, the EGD-2 promoter and theELF-1 promoter.

17. The polynucleotide of claim 14, wherein the activation domains are selected from the group consisting of at least one VP16 activation domain, at least one VP64 activation domain and at least one p65 activation domain.

18. The polynucleotide of claim 14, further comprising an internal ribosome entry site (IRES) disposed between the sequences encoding the first and second zinc finger proteins.

19. The polynucleotide of claim 14, further comprising a sequence encoding a 2A peptide disposed between the sequences encoding the first and second zinc finger proteins.

20. The polynucleotide of claim 14, wherein sequences encoding the second zinc finger protein are operably linked to a tumor-specific promoter.

21. The polynucleotide of claim 14, wherein sequences encoding the first and second zinc finger proteins are operably linked to a tumor-specific promoter.

22. The polynucleotide of claim 13, wherein the tumor specific promoter is selected from the group consisting of the E2F promoter, the survivin promoter, the human telomerase reverse transcriptase (hTERT) promoter, the COX-2 promoter, the EGD-2 promoter and theELF-1 promoter.

23. The polynucleotide of claim 14, wherein sequences encoding the first zinc finger protein are operably linked to a hypoxia-specific promoter.

24. The polynucleotide of claim 14, wherein sequences encoding the second zinc finger protein are operably linked to a hypoxia-specific promoter.

25. The polynucleotide of claim 14, wherein sequences encoding the first zinc finger protein are operably linked to a tissue-specific promoter.

26. The polynucleotide of claim 14, wherein sequences encoding the second zinc finger protein are operably linked to a tissue-specific promoter.