# US 10,570,394 B2 · Double-stranded RNA compounds to CASP2 and uses thereof

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

- Number: US 10,570,394 B2
- Document ID: US10570394B2
- Status: Granted
- Kind: B2
- Application number: 15/200,544
- Filed: 2016-07-01
- Published: 2016-10-20
- Granted: 2020-02-25
- Earliest claimed: 2012-01-04
- Assignees: Quark Pharmaceuticals, Inc.
- Applicants: Quark Pharmaceuticals, Inc.
- Inventors: Shai Erlich; James D. Thompson; Rabia Ozden; Elena Feinstein
- Web page: https://patentgrep.com/patent/US10570394B2

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61M 5/002: {Packages specially adapted therefor, e.g. packages for syringes or needles or kits for diabetics}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/02: for peripheral neuropathies
- A61P 27/02: Ophthalmic agents
- A61P 27/04: Artificial tears; Irrigation solutions
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- C12Y 304/22055: Caspase-2 (3.4.22.55)
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/317: with an inverted bond, e.g. a cap structure
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/34: Spatial arrangement of the modifications
- C12N 2310/344: Position-specific modifications, e.g. on every purine, at the 3'-end
- C12N 2310/3521: Methyl
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N 2320/35: based on a specific dosage / administration regimen
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES

## Abstract

The present disclosure relates to methods of treating a patient suffering from or at risk of developing an ocular disease, disorder or injury, and includes treatment regimens using a double-stranded RNA compound that down-regulates CASP2 expression, or a pharmaceutically acceptable salt thereof.

## Claims

### Claim 1

A method of treating a human patient suffering from or at risk for developing any one or more of primary open angle glaucoma (POAG), normal-tension glaucoma, primary angle-closure glaucoma (PACG), acute angle-closure glaucoma (AACG), angle-closure glaucoma, primary angle closure (PAC), or acute angle closure (AAC), the method comprising administering to the patient's eye via intravitreal (IVT) injection a double-stranded ribonucleic acid (dsRNA) compound that down-regulates CASP2 expression, wherein the double-stranded RNA compound has the structure:
(sense strand; SEQ ID NO: 1)
5′ iB - GCCAGAAUGUGGAACUCCU 3′
(antisense strand; SEQ ID NO: 2)
3′ CGGUCUUACACCUUGAGGA 5′
wherein each A, C, U, and G is a nucleotide and each consecutive nucleotide is joined to the next nucleotide by a phosphodiester bond;
wherein each nucleotide is independently an unmodified ribonucleotide, a 2′-O-Methyl sugar modified ribonucleotide, or an L-DNA nucleotide;
wherein the sense strand comprises, counting from the 5′ terminus, an unmodified ribonucleotide at each of positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 19 and a L-deoxycytidine at position 18, and an inverted abasic deoxyribose cap (iB) covalently bound to the 5′ terminus;
wherein the antisense strand comprises, counting from the 5′ terminus, a 2′-O-Methyl sugar modified ribonucleotide at each of positions 2, 4, 6, 8, 11, 13, 15, 17, and 19 and an unmodified ribonucleotide at each of positions 1, 3, 5, 7, 9, 10, 12, 14, 16, and 18;
or a pharmaceutically acceptable salt thereof; and
wherein the compound is administered to the patient's eye at a dose of about 1.2 mg to about 3.0 mg per eye.

### Claim 2 (depends on 1)

The method of claim 1, wherein the treatment comprises multiple administrations of the compound.

### Claim 3 (depends on 2)

The method of claim 2, wherein the IVT injections are administered six times.

### Claim 4 (depends on 2)

The method of claim 2, wherein the multiple administrations occur at regular intervals.

### Claim 5 (depends on 2)

The method of claim 2, wherein the compound is administered as six IVT injections at intervals about one month apart.

### Claim 6 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt is a sodium salt.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound is administered to the patient's eye as a liquid composition comprising a pharmaceutically acceptable carrier.

### Claim 8 (depends on 7)

The method according to claim 7, wherein a volume of a single dose IVT injection is between about 20 μl to about 200 μl.

### Claim 9 (depends on 7)

The method according to claim 7, wherein a volume of a single dose IVT injection is between about 50 μl to about 100 μl.