# US 2020/0399640 A1 · Treatment of angiopoietin like 7 (angptl7) related diseases

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- Number: US 2020/0399640 A1
- Document ID: US20200399640A1
- Status: Published application
- Kind: A1
- Application number: 17/012,524
- Filed: 2020-09-04
- Published: 2020-12-24
- Earliest claimed: 2019-05-24
- Assignees: Empirico Inc.
- Applicants: Empirico Inc.
- Inventors: Omri GOTTESMAN; Shannon BRUSE; Paul BUSKE; Brian CAJES; David LEWIS; David ROZEMA
- Web page: https://patentgrep.com/patent/US20200399640A1

## CPC

- C12N 15/1136: {against growth factors, growth regulators, cytokines, lymphokines or hormones}
- A61P 27/06: Antiglaucoma agents or miotics
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/322: 2'-R Modification
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/343: having patterns, e.g. ==--==--==--
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2310/3515: Lipophilic moiety, e.g. cholesterol
- 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

## Abstract

Provided herein are oligonucleotide compositions that inhibit ANGPTL7 and reduce intraocular pressure when administered to an eye. The oligonucleotide compositions contain nucleoside modifications.

## Claims

### Claim 1

A composition comprising an oligonucleotide that targets Angiopoietin like 7 (ANGPTL7) and when administered to a cell decreases expression of ANGPTL7, wherein the oligonucleotide comprises a small interfering RNA (siRNA) comprising a sense strand and an antisense strand, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NOs: 1424, 1541, 2091 in which at least one internucleoside linkage is modified and at least one base is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside, substitutions, additions, or deletions of SEQ ID NOs: 1424, 1541, or 2091 in which at least one internucleoside linkage is modified and at least one base is modified, and wherein the antisense strand comprises an oligonucleotide sequence of SEQ ID NOs: 3630, 3747, or 4297 in which at least one internucleoside linkage is modified and at least one base is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside, substitutions, additions, or deletions of SEQ ID NOs: 3630, 3747, or 4297 in which at least one internucleoside linkage is modified and at least one base is modified.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the at least one base is modified comprises a nucleoside base modification to a 2′ fluoro modified nucleoside.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the at least one base is modified comprises a nucleoside base modification to a 2′ O-methyl modified nucleoside.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the oligonucleotide comprises 15-23 modified nucleosides.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the 15-23 modified nucleosides comprises 2′ fluoro modified nucleosides and 2′ O-methyl modified nucleosides.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the at least one internucleoside linkage is modified comprises a modification to a phosphorothioate linkage.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the oligonucleotide comprises a lipid attached at a 3′ or 5′ terminus of the oligonucleotide.

### Claim 8 (depends on 7)

The composition of claim 7, wherein the lipid comprises cholesterol, myristoyl, palmitoyl, stearoyl, lithocholoyl, docosanoyl, docosahexaenoyl, myristyl, palmityl stearyl, or α-tocopherol, or a combination thereof.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the lipid is attached to the 3′ terminus of the sense strand.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the lipid comprises cholesterol.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NO: 11186 and the antisense strand comprises an oligonucleotide sequence of SEQ ID NO: 11306.

### Claim 12 (depends on 10)

The composition of claim 10, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NO: 11200 and the antisense strand comprises an oligonucleotide sequence of SEQ ID NO: 11320.

### Claim 13 (depends on 10)

The composition of claim 10, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NO: 11211 and the antisense strand comprises an oligonucleotide sequence of SEQ ID NO: 11331.

### Claim 14

A pharmaceutical composition comprising
(a) an oligonucleotide that targets Angiopoietin like 7 (ANGPTL7) and when administered to a cell decreases expression of ANGPTL7, wherein the oligonucleotide comprises a small interfering RNA (siRNA) comprising a sense strand and an antisense strand, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NOs: 1424, 1541, 2091 in which at least one internucleoside linkage is modified and at least one base is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside, substitutions, additions, or deletions of SEQ ID NOs: 1424, 1541, or 2091 in which at least one internucleoside linkage is modified and at least one base is modified, and wherein the antisense strand comprises an oligonucleotide sequence of SEQ ID NOs: 3630, 3747, or 4297 in which at least one internucleoside linkage is modified and at least one base is modified, or an oligonucleotide sequence comprising 1 or 2 nucleoside, substitutions, additions, or deletions of SEQ ID NOs: 3630, 3747, or 4297 in which at least one internucleoside linkage is modified and at least one base is modified; and
(b) a pharmaceutically acceptable carrier.

### Claim 15

A composition comprising an oligonucleotide that targets Angiopoietin like 7 (ANGPTL7) and when administered to a subject in an effective amount decreases intraocular pressure, wherein the oligonucleotide comprises a small interfering RNA (siRNA) comprising a sense strand and an antisense strand, the antisense strand being complementary to a portion of a nucleic acid having the nucleoside sequence of SEQ ID NO: 11085, and each strand having 14 to 30 nucleotides, and wherein the oligonucleotide comprises a lipid attached at a 3′ or 5′ terminus of the oligonucleotide.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the lipid is attached to the 3′ terminus of the sense strand.

### Claim 17 (depends on 16)

The composition of claim 16, wherein the lipid comprises cholesterol.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NO: 11186 and the antisense strand comprises an oligonucleotide sequence of SEQ ID NO: 11306.

### Claim 19 (depends on 17)

The composition of claim 17, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NO: 11200 and the antisense strand comprises an oligonucleotide sequence of SEQ ID NO: 11320.

### Claim 20 (depends on 17)

The composition of claim 17, wherein the sense strand comprises an oligonucleotide sequence of SEQ ID NO: 11211 and the antisense strand comprises an oligonucleotide sequence of SEQ ID NO: 11331.