# US 7,745,612 B2 · siRNA targeting interleukin-1 receptor-associated kinase 4 (IRAK4)

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- Number: US 7,745,612 B2
- Document ID: US7745612B2
- Status: Granted
- Kind: B2
- Application number: 12/462,029
- Filed: 2009-07-28
- Published: 2009-12-31
- Granted: 2010-06-29
- Earliest claimed: 2002-11-14
- Assignees: Dharmacon, Inc.
- Inventors: Anastasia Khvorova; Angela Reynolds; Devin Leake; William Marshall; Steven Read; Stephen Scaringe
- Web page: https://patentgrep.com/patent/US7745612B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/11: for the determination of target sites, i.e. of active nucleic acids
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for IRAK4.

## Claims

### Claim 1

An siRNA molecule, wherein said siRNA molecule consists of: (a) a duplex region; and (b) either no overhangs regions or at least one overhang region, wherein each overhang region comprises six or fewer nucleotides, wherein the duplex region consists of a sense region and an antisense region, wherein said sense region and said antisense region together form said duplex region and said duplex region is 19-30 base pairs in length and said antisense region comprises a sequence that is the complement of SEQ ID NO: 540.

### Claim 2 (depends on 1)

The siRNA molecule of claim 1, wherein said antisense region and said sense region are each 19-25 bases in length.

### Claim 3 (depends on 2)

The siRNA molecule of claim 2, wherein said antisense region and said sense region are each 19 bases in length.

### Claim 4 (depends on 1)

The siRNA molecule of claim 1, wherein said siRNA molecule has at least one overhang region.

### Claim 5 (depends on 2)

The siRNA molecule of claim 2, wherein said siRNA molecule has no overhang regions.

### Claim 6 (depends on 2)

The siRNA molecule of claim 2, wherein said siRNA molecule has at least one overhang region.

### Claim 7 (depends on 2)

The siRNA molecule of claim 2, wherein said siRNA molecule has no overhang regions.

### Claim 8 (depends on 3)

The siRNA molecule of claim 3, wherein said siRNA molecule has at least one overhang region.

### Claim 9 (depends on 3)

The siRNA molecule of claim 3, wherein said siRNA molecule has no overhang regions.

### Claim 10

A chemically synthesized double-stranded siRNA molecule, wherein:
(a) each strand of said siRNA molecule is between 19 and 30 nucleotides in length; and
(b) one strand of said siRNA molecule comprises a sequence that is the complement of SEQ ID NO: 540.

### Claim 11 (depends on 10)

The chemically synthesized double-stranded siRNA molecule of claim 10, wherein each strand of said siRNA molecule is 19 nucleotides in length.

### Claim 12 (depends on 1)

A pool of at least two siRNAs, wherein said pool comprises a first siRNA and a second siRNA, wherein said first siRNA is the siRNA molecule of claim 1 and the duplex region of said first siRNA is a first duplex region and said second siRNA consists of a second duplex region and either no overhang regions or at least one overhang region, wherein each overhang region comprises six or fewer nucleotides, wherein the second duplex region of said second siRNA consists of a second sense region and a second antisense region, wherein said second sense region and said second antisense region together form said second duplex region and said second duplex region is 19-30 base pairs in length and said second antisense region comprises a sequence that is the complement of a sequence selected from the group consisting of SEQ ID NO. 438-539, 541-569 and 571-614.

### Claim 13 (depends on 12)

The pool of claim 12, wherein said first siRNA and said second siRNA each have no overhang regions.

### Claim 14 (depends on 12)

The pool of claim 12, wherein said first duplex region and said second duplex region are each 19-25 base pairs in length.

### Claim 15 (depends on 14)

The pool of claim 14, wherein said first duplex region and said second duplex region are each 19 base pairs in length.

### Claim 16 (depends on 15)

The pool of claim 15, wherein said first siRNA molecule contains no overhang regions.

### Claim 17 (depends on 16)

The pool of claim 16, wherein the second siRNA molecule contains no overhang regions.

### Claim 18 (depends on 15)

The pool of claim 15, wherein the first siRNA molecule contains at least one overhang region.

### Claim 19 (depends on 18)

The pool of claim 18, wherein the siRNA molecule contains at least one overhang region.

### Claim 20

An siRNA molecule consisting of:
(a) a duplex region; and
(b) either no overhang regions or at least one overhang region, wherein each overhang region comprises six or fewer nucleotides,
wherein the duplex region is nineteen base pairs in length and consists of a sense region that has a sequence that is the same as SEQ ID NO: 540 and an antisense region that has a sequence that is the complement of SEQ ID NO: 540.
