# US 2023/0057461 A1 · Rab13 and net1 antisense oligonucleotides to treat metastatic cancer

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- Number: US 2023/0057461 A1
- Document ID: US20230057461A1
- Status: Published application
- Kind: A1
- Application number: 17/792,507
- Filed: 2021-01-26
- Published: 2023-02-23
- Earliest claimed: 2020-01-27
- Assignees: The U.S.A., as represented by the Secretary, Department of Health and Human Services
- Applicants: The U.S.A., as represented by the Secretary, Department of Health and Human Services
- Inventors: Stavroula Mili
- Web page: https://patentgrep.com/patent/US20230057461A1

## CPC

- A61K 31/712: Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
- 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 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/7125: Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/04: specific for metastasis
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/3233: Morpholino-type ring
- 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)
- 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 antisense oligonucleotides (ASOs) specific for Rab13 and Net1, for example specific for a GA-rich region of the 3′-UTR. In some examples, the ASOs are modified. Methods of using these ASOs to reduce the migration of metastatic cancer cells are provided, for example as a use to treat metastatic cancer.

## Claims

### Claim 1

(canceled)

### Claim 2

An isolated antisense oligonucleotide (ASO) no more than 28 nucleotides in length, comprising the sequence of any one of SEQ ID NO: 8, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 30, SEQ ID NO: 31 and SEQ ID NO: 32, wherein:
the ASO comprises one or more chemical modifications;
a detectable label is covalently attached to the ASO; and/or
a nanoparticle is covalently attached to the ASO.

### Claim 3 (depends on 2)

The isolated ASO of claim 2, wherein the sequence of the ASO consists of the sequence of any one of SEQ ID NO: 8, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 30, SEQ ID NO: 31 and SEQ ID NO: 32.

### Claim 4 (depends on 2)

The isolated ASO of claim 2, wherein the ASO comprises one or more chemical modifications.

### Claim 5 (depends on 4)

The isolated ASO of claim 4, wherein the one or more chemical modifications comprises at least one phosphorothioate, at least one 2′-fluoro, at least one 2′-β-methyl, at least one 2′-β-methoxy-ethyl, at least one morpholino, at least one 2′,4′-constrained ethyl nucleic acid, and/or at least one locked nucleic acid (LNA).

### Claim 6 (depends on 2)

The isolated ASO of claim 2, wherein a detectable label is covalently attached to the ASO.

### Claim 7 (depends on 2)

The isolated ASO of claim 2, wherein a nanoparticle is covalently attached to the ASO.

### Claim 8 (depends on 7)

The isolated ASO of claim 7, wherein the nanoparticle comprises a polymeric nanoparticle, nanosphere, nanocapsule, liposome, dendrimer, polymeric micelle, or niosome.

### Claim 9 (depends on 2)

A cell comprising the isolated ASO of claim 2.

### Claim 10 (depends on 8)

The cell of claim 8, wherein the cell is a bacterial cell or mammalian cell.

### Claim 11 (depends on 2)

A composition comprising one or more isolated ASOs of claim 2, and a pharmaceutically acceptable carrier.

### Claim 12 (depends on 2)

A method of treating a metastatic tumor, comprising:
administering a therapeutically effective amount of one or more of the isolated ASOs of claim 2 to a subject with the metastatic tumor, thereby treating the metastatic tumor.

### Claim 13 (depends on 12)

The method of claim 12, wherein the method reduces a number of metastases of the metastatic tumor, reduces the size of a metastasis, reduces the volume of a metastasis, or combinations thereof.

### Claim 14 (depends on 12)

The method of claim 12, wherein the administering is intratumoral.

### Claim 15 (depends on 2)

A method of reducing migration of a cell, comprising:
contacting a cell with a therapeutically effective amount of one or more of the isolated ASOs of claim 2, thereby reducing migration of the cell.

### Claim 16 (depends on 15)

The method of claim 15, wherein the method reduces a migration speed of the cell, protrusion velocity of the cell, retraction velocity of the cell, or combinations thereof.

### Claim 17 (depends on 15)

The method of claim 15, wherein the cell is a metastatic tumor cell.

### Claim 18 (depends on 12)

The method of claim 12, wherein the metastatic tumor is a tumor of the breast, lung, colon, pancreas, ovary, uterus, cervix, skin, prostate, bone, central nervous system, kidney, or head and neck.

### Claim 19 (depends on 15)

The method of claim 15, wherein the cell is in a subject, and contacting comprises administration to the subject.

### Claim 20 (depends on 12)

The method of claim 12, further comprising administering a therapeutically effective amount of an additional anti-cancer agent to the subject.

### Claim 21 (depends on 20)

The method of claim 20, wherein the anti-cancer agent comprises a chemotherapeutic, radiation therapy, and/or a biologic.