# US 2019/0169620 A1 · Treatment of HER2-Dependent Cancers by SORL1 Inhibition

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- Number: US 2019/0169620 A1
- Document ID: US20190169620A1
- Status: Published application
- Kind: A1
- Application number: 16/146,448
- Filed: 2018-09-28
- Published: 2019-06-06
- Earliest claimed: 2017-12-01
- Assignees: Turun Yliopisto
- Applicants: Turun Yliopisto
- Inventors: Mika PIETILÄ; Johanna IVASKA; Pranshu SAHGAL
- Web page: https://patentgrep.com/patent/US20190169620A1

## CPC

- C12N 15/1138: {against receptors or cell surface proteins}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 2310/122: Hairpin
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2800/80: Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
- 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

This disclosure relates to the field of cancer therapeutics. Exemplary embodiments relate to agents that inhibit expression of SORL1, a gene encoding for Sortilin related protein family-A (SORLA) or the function of SORLA protein, a multifunctional protein belonging to sortilin and LDL-receptor families, and to methods for their use in treating HER2-dependent cancers.

## Claims

### Claim 1

A composition comprising:
a SORL1 inhibiting agent, selected for treating HER2-dependent cancer; and
a drug selected from the group consisting of cationic amphiphilic drugs (CAD) and HER2-targeted drugs.

### Claim 2 (depends on 1)

The agent according to claim 1, wherein said agent inhibits SORL1 gene expression.

### Claim 3 (depends on 2)

The agent according to claim 2, wherein said agent is selected from the group consisting of siRNA molecules, shRNA molecules, DsiRNA molecules, artificial miRNA precursors, and antisense oligonucleotides.

### Claim 4 (depends on 3)

The agent according to claim 3, wherein said agent is siRNA comprising:
a sequence selected from the group consisting of SEQ ID Nos: 1-18.

### Claim 5 (depends on 3)

The agent according to claim 3, wherein said agent is shRNA comprising:
a sequence selected from the group consisting of SEQ ID Nos: 19 and 20.

### Claim 6 (depends on 1)

The agent according to claim 1, wherein said agent is a gene editing agent.

### Claim 7 (depends on 6)

The agent according to claim 6, wherein said agent comprises:
a polynucleotide encoding CRISPR associated protein 9 (Cas9); and
a guide nucleotide sequence directing Cas9 nuclease to an SORL1 gene region.

### Claim 8 (depends on 7)

The agent according to claim 7, wherein said guide nucleotide sequence comprises:
a sequence selected from the group consisting of SEQ ID Nos: 21-51.

### Claim 9 (depends on 1)

The agent according to claim 1, wherein said agent is an antibody.

### Claim 10 (depends on 9)

The agent according to claim 9, wherein said antibody binds to an SORL1 extracellular domain and disrupts association between SORL1 and HER2.

### Claim 11 (depends on 9)

The agent according to claim 9, wherein said antibody is a dual-specificity antibody binding simultaneously to SORL1 and HER2.

### Claim 12 (depends on 1)

The agent according to claim 1, wherein said cancer is selected from the group consisting of breast cancer, ovarian cancer, gastric cancer, colorectal cancer, bladder cancer and any cancer that is HER2-dependent.

### Claim 13

(canceled)

### Claim 14

(canceled)

### Claim 15

Method for treating HER2-dependent cancer, the method comprising:
administering a therapeutically effective amount of an SORL1 inhibiting agent to a subject in need thereof.

### Claim 16 (depends on 15)

The method according to claim 15, wherein said agent inhibits SORL1 gene expression.

### Claim 17 (depends on 16)

The method according to claim 16, wherein said agent is selected from the group consisting of siRNA molecules, shRNA molecules, DsiRNA molecules, artificial miRNA precursors, and antisense oligonucleotides.

### Claim 18 (depends on 17)

The method according to claim 17, wherein said agent is siRNA comprising:
a sequence selected from the group consisting of SEQ ID Nos: 1-18.

### Claim 19 (depends on 15)

The method according to claim 15, wherein said agent is a gene editing agent.

### Claim 20 (depends on 19)

The method according to claim 19, wherein said agent comprises:
a polynucleotide encoding CRISPR associated protein 9 (Cas9); and
a guide nucleotide sequence directing Cas9 nuclease to an SORL1 gene reg