# US 2008/0187523 A1 · Anti-angiogenic methods and compositions

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2008/0187523 A1
- Document ID: US20080187523A1
- Status: Published application
- Kind: A1
- Application number: 11/999,549
- Filed: 2007-12-06
- Published: 2008-08-07
- Earliest claimed: 2005-02-28
- Assignees: Sangamo BioSciences, Inc.
- Inventors: H. Steve Zhang; Philip D. Gregory
- Web page: https://patentgrep.com/patent/US20080187523A1

## CPC

- C07K 14/4705: {stimulating, promoting or activating activity}
- A61P 27/02: Ophthalmic agents
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/4702: {Regulators; Modulating activity}
- C07K 14/811: {Serine protease (E.C. 3.4.21) inhibitors}
- 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)
- C07K 2319/71: containing domain for transcriptional activaation, e.g. VP16
- C07K 2319/81: containing a Zn-finger domain for DNA binding
- C12N 2799/022: where the vector is derived from an adenovirus
- C12N 2799/025: where the vector is derived from a parvovirus
- C12N 2799/028: where the vector is derived from a herpesvirus
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## 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

### Claim 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:
F1:
RSDALSR
(SEQ ID NO:14)
F2:
QSGDLTR
(SEQ ID NO:15)
F3:
QSGDLTR
(SEQ ID NO:15)
F4:
TSGHLSR
(SEQ ID NO:16)
F5:
RSDHLSN
(SEQ ID NO:17)
F6:
QSATRIT;
(SEQ ID NO:18)
and
wherein the second zinc finger protein comprises three zinc fingers and the amino acid sequence of the recognition region of each of the zinc fingers is as follows:
F1:
DRSNLTR
(SEQ ID NO: 83)
F2:
TSGHLSR
(SEQ ID NO: 16)
F3:
RSDHLSR.
(SEQ ID NO: 84)

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 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:
F1:
RSDALSR
(SEQ ID NO:14)
F2:
QSGDLTR
(SEQ ID NO:15)
F3:
QSGDLTR
(SEQ ID NO:15)
F4:
TSGHLSR
(SEQ ID NO:16)
F5:
RSDHLSN
(SEQ ID NO:17)
F6:
QSATRIT;
(SEQ ID NO:18)
and
wherein the second 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:
F1:
RSDALSE
(SEQ ID NO:65)
F2:
DSSHRTR
(SEQ ID NO:60)
F3:
RSDHLSA
(SEQ ID NO:61)
F4:
ANSNRIK
(SEQ ID NO:62)
F5:
QSSDLSR
(SEQ ID NO:58)
F6:
RSDALAR.
(SEQ ID NO:32)

### Claim 5 (depends on 4)

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.

### Claim 6 (depends on 4)

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.

### Claim 7 (depends on 4)

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

### Claim 8 (depends on 4)

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

### Claim 9 (depends on 4)

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

### Claim 10 (depends on 7)

The polynucleotide of claim 7, 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 the ELF-1 promoter.

### Claim 11 (depends on 4)

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

### Claim 12 (depends on 4)

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

### Claim 13 (depends on 4)

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

### Claim 14 (depends on 4)

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

### Claim 15 (depends on 4)

A method for the treatment of a malignancy in an organism, wherein the method comprises introducing the polynucleotide of claim 4 into one or more cells of the organism.

### Claim 16 (depends on 10)

A method for the treatment of a malignancy in an organism, wherein the method comprises introducing the polynucleotide of claim 10 into one or more cells of the organism.

### Claim 17 (depends on 15)

The method of claim 15, in which the polynucleotide is introduced into a tumor.

### Claim 18 (depends on 15)

The method of claim 15, in which the polynucleotide is introduced into an endothelial or mesenchymal stem cell and the stem cell is subsequently introduced into the organism.

### Claim 19 (depends on 15)

The method of claim 15, in which the polynucleotide is encapsidated in a viral delivery vehicle selected from the group consisting of adeno-associated virus (AAV), Adenovirus and Herpes simplex virus.

### Claim 20 (depends on 19)

The method of claim 19, in which the viral delivery vehicle is an Adenovirus.

### Claim 21 (depends on 20)

The method of claim 20, wherein the adenovirus replicates preferentially in tumor cells.

### Claim 22 (depends on 20)

The method of claim 20, in which the adenovirus vector is a non-replicating adenovirus vector.

### Claim 23 (depends on 22)

The method of claim 22, in which the viral vector is Adenovirus Type 5.

### Claim 24 (depends on 15)

The method of claim 15, wherein the organism is a human.

### Claim 25 (depends on 15)

The method of claim 15, wherein the malignancy occurs in a disease selected from the group consisting of head and neck cancer, glioblastoma, prostate cancer and pancreatic cancer.