# US 2010/0168207 A1 · Compositions and methods for sirna inhibition of angiogenesis

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- Number: US 2010/0168207 A1
- Document ID: US20100168207A1
- Status: Published application
- Kind: A1
- Application number: 12/636,075
- Filed: 2009-12-11
- Published: 2010-07-01
- Earliest claimed: 2002-07-24
- Assignees: The Trustees of the University of Pennsylvania
- Inventors: Michael Jotham Tolentino; Samuel J. Reich
- Web page: https://patentgrep.com/patent/US20100168207A1

## CPC

- C12N 15/1136: {against growth factors, growth regulators, cytokines, lymphokines or hormones}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity}
- C12N 15/1138: {against receptors or cell surface proteins}
- C12N 15/86: Viral vectors
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- 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)
- C12N 2310/111: spanning the whole gene, or a large part of it
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/53: partially self-complementary or closed
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2320/51: modulating the chemical stability, e.g. nuclease-resistance
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

RNA interference using small interfering RNAs which are specific for the vascular endothelial growth factor (VEGF) gene and the VEGF receptor genes Flt-1 and Flk-1/KDR inhibit expression of these genes. Diseases which involve angiogenesis stimulated by overexpression of VEGF, such as diabetic retinopathy, age related macular degeneration and many types of cancer, can be treated by administering the small interfering RNAs.

## Claims

### Claim 1

An isolated siRNA comprising of a duplex of a first RNA strand and a second RNA strand, said first RNA strand comprising a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in said human VEGF mRNA.

### Claim 2 (depends on 1)

The siRNA of claim 1, wherein said human VEGF mRNA is selected from VEGF121 mRNA (SEQ ID NO: 2); VEGF165 mRNA (SEQ ID NO: 3); VEGF189 mRNA (SEQ ID NO: 4) and VEGF206 mRNA (SEQ ID NO: 5).

### Claim 3 (depends on 1)

The siRNA of claim 1, wherein the first and second RNA strands forming the RNA duplex are covalently linked by a single-stranded hairpin.

### Claim 4 (depends on 1)

The siRNA of claim 1, wherein the siRNA further comprises non-nucleotide material.

### Claim 5 (depends on 1)

The siRNA of claim 1, wherein the first and second RNA strands are stabilized against nuclease degradation.

### Claim 6 (depends on 1)

The siRNA of claim 1, further comprising a 3′ overhang.

### Claim 7 (depends on 6)

The siRNA of claim 6, wherein the 3′ overhang comprises from 1 to about 6 nucleotides.

### Claim 8 (depends on 6)

The siRNA of claim 6, wherein the 3′ overhang comprises about 2 nucleotides.

### Claim 9 (depends on 1)

The siRNA of claim 1, wherein the sense RNA strand comprises a first 3′ overhang, and the antisense RNA strand comprises a second 3′ overhang.

### Claim 10 (depends on 9)

The siRNA of claim 9, wherein the first and second 3′ overhangs each comprise from 1 to about 6 nucleotides.

### Claim 11 (depends on 9)

The siRNA of claim 9, wherein the first 3′ overhang comprises a dinucleotide and the second 3′ overhang comprises a dinucleotide.

### Claim 12 (depends on 11)

The siRNA of claim 11, where the dinucleotide comprising the first and second 3′ overhangs is dithymidylic acid (TT) or diuridylic acid (uu).

### Claim 13 (depends on 6)

The siRNA of claim 6, wherein the 3′ overhang is stabilized against nuclease degradation.

### Claim 14

A pharmaceutical composition comprising a siRNA and a pharmaceutically acceptable carrier, said siRNA comprised of a duplex of a first RNA strand and a second RNA strand, said first RNA strand comprising a nucleotide sequence identical to a target sequence of about 19 to about 25 contiguous nucleotides in said human VEGF mRNA.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, wherein said human VEGF mRNA is selected from VEGF121 mRNA (SEQ ID NO: 2); VEGF165 mRNA (SEQ ID NO: 3); VEGF189 mRNA (SEQ ID NO: 4) and VEGF206 mRNA (SEQ ID NO: 5).

### Claim 16 (depends on 14)

The pharmaceutical composition of claim 14, wherein the first and second RNA strands are stabilized against nuclease degradation.

### Claim 17 (depends on 14)

The pharmaceutical composition of claim 14, further comprising at least one 3′ overhang.

### Claim 18 (depends on 17)

The pharmaceutical composition of claim 17, wherein the at least one 3′ overhang comprises about 2 nucleotides.

### Claim 19 (depends on 17)

The pharmaceutical composition of claim 17, where the at least one 3′ overhang comprises a dithymidylic acid (TT) or diuridylic acid (uu).

### Claim 20 (depends on 14)

The pharmaceutical composition of claim 14, wherein the sense RNA strand comprises a first 3′ overhang, and the antisense RNA strand comprises a second 3′ overhang.