# US 9,752,147 B2 · RNAi-mediated inhibition of connexin 43 for treatment of IOP-related conditions

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- Number: US 9,752,147 B2
- Document ID: US9752147B2
- Status: Granted
- Kind: B2
- Application number: 15/277,058
- Filed: 2016-09-27
- Published: 2017-01-12
- Granted: 2017-09-05
- Earliest claimed: 2008-02-15
- Assignees: Arrowhead Pharmaceuticals, Inc.
- Applicants: Arrowhead Pharmaceuticals, Inc.
- Inventors: Jon E. Chatterton; Abbot F. Clark; Martin B. Wax
- Web page: https://patentgrep.com/patent/US9752147B2

## 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)}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- C12N 15/1138: {against receptors or cell surface proteins}
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/30: Special therapeutic applications
- 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 is provided for inhibition of connexin 43 (Cx43) in intraocular pressure-related conditions, including ocular hypertension and glaucoma such as normal tension glaucoma and open angle glaucoma.

## Claims

### Claim 1

An interfering RNA for inhibiting the expression of a connexin 43 (Cx43) gene, wherein the interfering RNA comprises a sense strand and an antisense strand each 19-49 nucleotides in length, wherein the sense strand comprises a nucleotide sequence of SEQ ID NO:13, except that each T can be independently replaced with a U, and the antisense strand comprises a nucleotide sequence that is complementary to the sense strand.

### Claim 2 (depends on 1)

The interfering RNA of claim 1, wherein each strand of the interfering RNA is 19 to 27 nucleotides in length.

### Claim 3 (depends on 2)

The interfering RNA of claim 2, wherein the interfering RNA comprises one or more chemically modified nucleotides, one or more non-nucleotides, one or more deoxyribonucleotides, and/or one or more non-phosphodiester linkages.

### Claim 4 (depends on 3)

The interfering RNA of claim 3, wherein the interfering RNA comprises one or more chemically modified nucleotides having a 2′ amino group, a 2′ O-methyl group, a 2′ methoxyethyl group, or a 2′-O,4′-C methylene bridge.

### Claim 5 (depends on 3)

The interfering RNA of claim 3, wherein the interfering RNA comprises one or more chemically modified nucleotides and one or more non-phosphodiester linkages.

### Claim 6 (depends on 3)

The interfering RNA of claim 3, wherein non-nucleotide material is bound to the 5′ end and/or 3′ end of the sense strand and/or the 3′ end of the antisense strand.

### Claim 7 (depends on 6)

The interfering RNA of claim 6, wherein the non-nucleotide material is bound internally to the sense strand and/or the antisense strand.

### Claim 8 (depends on 6)

The interfering RNA of claim 6, wherein the non-nucleotide material improves cellular uptake, enhances cellular targeting, assists in tracing, improves stability, and/or reduces activation of the interferon pathway.

### Claim 9 (depends on 3)

The interfering RNA of claim 3, wherein the sense strand and/or the antisense strand contains a 3′ overhang.

### Claim 10 (depends on 3)

The interfering RNA of claim 3, wherein the sense strand contains a 5′ overhang.

### Claim 11 (depends on 3)

The interfering RNA of claim 3, wherein the interfering RNA comprises at least one blunt end.

### Claim 12 (depends on 1)

A composition for inhibiting the expression of a connexin 43, the composition comprising the interfering RNA of claim 1 and a pharmaceutically acceptable carrier.

### Claim 13 (depends on 12)

The composition of claim 12, wherein the interfering RNA comprises one or more chemically modified nucleotides, one or more non-nucleotides, one or more deoxyribonucleotides, and/or one or more non-phosphodiester linkages.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the interfering RNA comprises one or more chemically modified nucleotides having a 2′ amino group, a 2′ O-methyl group, a 2′ methoxyethyl group, or a 2′-O,4′-C methylene bridge.

### Claim 15 (depends on 13)

The composition of claim 13, wherein the interfering RNA comprises one or more chemically modified nucleotides and one or more non-phosphodiester linkages.

### Claim 16 (depends on 13)

The composition of claim 13, wherein non-nucleotide material is bound to the 5′ end and/or 3′ end of the sense strand and/or the antisense strand.

### Claim 17 (depends on 13)

The composition of claim 13, wherein the non-nucleotide material is bound internally to the sense strand and/or the antisense strand.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the non-nucleotide material improves cellular uptake, enhances cellular targeting, assists in tracing, improves stability, and/or reduces activation of the interferon pathway.

### Claim 19 (depends on 13)

The composition of claim 13, wherein the sense strand and/or the antisense strand contains a 3′ overhang.

### Claim 20 (depends on 13)

The composition of claim 13, wherein the sense strand and/or the antisense strand contains a 5′ overhang.

### Claim 21 (depends on 13)

The composition of claim 13, wherein the interfering RNA molecule comprises at least one blunt end.