# US 2019/0375808 A1 · ANALOGUES OF VDAC1-DERlVED PEPTIDES

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- Number: US 2019/0375808 A1
- Document ID: US20190375808A1
- Status: Published application
- Kind: A1
- Application number: 16/451,520
- Filed: 2019-06-25
- Published: 2019-12-12
- Earliest claimed: 2015-09-03
- Assignees: B. G. Negev Technologies and Applications Ltd., At Ben-Gurion University; The National Institute for Biotechnology In the Negev Ltd.
- Applicants: B. G. Negev Technologies and Applications Ltd., At Ben-Gurion University; The National Institute for Biotechnology In the Negev Ltd.
- Inventors: Varda Shoshan-Barmatz
- Web page: https://patentgrep.com/patent/US20190375808A1

## CPC

- C07K 14/4747: {Apoptosis related proteins}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07K 14/79: Transferrins, e.g. lactoferrins, ovotransferrins
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention relates to peptides comprising analogues of VDAC1-derived peptides having improved pharmacokinetic characteristics compared to the native parent peptides, which are effective in impairing cell energy production, in inducing apoptosis and cell death, particularly of cancerous cells, in eliminating cancer stem cells and in reducing symptoms associated with fat accumulation in liver cells particularly with nonalcoholic fatty liver disease (NAFLD) and symptoms associated thereto

## Claims

### Claim 1

A method for treating a disease associated with aberrant apoptosis and/or cell hyper-proliferation, the method comprises administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising at least one synthetic peptide, the synthetic peptide comprising an analogue of VDAC1-derived peptide, the VDAC1-derived peptide is capable of inducing apoptosis in cancerous cells and consists of 5-26 contiguous amino acids, wherein the analogue is retro modified and partially or completely inverso modified with respect to the VDAC1-derived peptide, thereby treating the disease associated with aberrant apoptosis and/or cell hyper-proliferation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the VDAC1-derived peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:4.

### Claim 3 (depends on 1)

The method of claim 1, wherein the analogue comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:5.

### Claim 4 (depends on 3)

The method of claim 3, wherein the analogue is completely inverso modified, said analogue comprises an amino acid sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:6.

### Claim 5 (depends on 1)

The method of claim 1, wherein the synthetic peptide further comprises a cell recognition and/or localization moiety selected from all L-stereomeric peptide and all D-stereomeric peptide.

### Claim 6 (depends on 5)

The method of claim 5, wherein the recognition and/or localization peptide comprises transferrin-receptor binding domain (TO, a retro-analogue of the transferrin-receptor binding domain (TO, or a fragment thereof.

### Claim 7 (depends on 6)

The method of claim 6, wherein the transferrin-receptor binding domain has the amino acids sequence set forth in SEQ ID NO:7 and the retro-analogue of transferrin-receptor binding domain (TO has the amino acids sequence set forth in SEQ ID NO:8.

### Claim 8 (depends on 7)

The method of claim 7, wherein the synthetic peptide comprises (i) an analogue comprising the amino acid sequence set forth in SEQ ID NO:3 and (ii) a recognition and/or localization peptide comprising the amino acid sequence set forth in SEQ ID NO:8.

### Claim 9 (depends on 5)

The method of claim 5, wherein the recognition and/or localization peptide is connected to the N- or the C-terminus of the analogue of VDAC1-derived peptide directly or via a linker sequence.

### Claim 10 (depends on 9)

The method of claim 9, wherein the synthetic peptide further comprises the amino acids sequences set forth in SEQ ID NO:11 and the amino acid sequence set forth SEQ NO:12, each independently located at the C- or N-terminus of the analogue of VDAC1-derived peptide.

### Claim 11 (depends on 9)

The method of claim 9, wherein the synthetic peptide further comprises the amino acids sequences set forth in SEQ ID NO:12 and the amino acid sequence set forth in SEQ ID NO:13, each independently located at the C- or N-terminus of the analogue of VDAC1-derived peptide.

### Claim 12 (depends on 11)

The method of claim 11, wherein the synthetic peptide comprises the amino acid sequence set forth in SEQ ID NO:14.

### Claim 13 (depends on 5)

The method of claim 5, wherein the recognition and/or localization peptide comprises Antp domain, a retro-analogue of the Antp domain or a fragment thereof.

### Claim 14 (depends on 13)

The method of claim 13, wherein the synthetic peptide comprises the amino acid sequence set forth in any one of SEQ ID NO:15 and SEQ ID NO:16.

### Claim 15 (depends on 1)

The method of claim 1, wherein the disease is a cancerous disease.

### Claim 16 (depends on 15)

The method of claim 15, wherein the cancerous disease is selected from the group consisting of glioma, liver cancer, leukemia, lung cancer, prostate cancer, breast cancer, pancreas cancer and melanoma.

### Claim 17

A method of treating and/or preventing non-alcoholic fatty liver disease (NAFLD) and/or a symptom associated with NAFLD, comprising administrating to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition comprising at least one synthetic peptide, the synthetic peptide comprising an analogue of VDAC1-derived peptide, the VDAC1-derived peptide is capable of inducing apoptosis in cancerous cells and consists of 5-26 contiguous amino acids, wherein the analogue is retro modified and partially or completely inverso modified with respect to the VDAC1-derived peptide, thereby treating and/or preventing the non-alcoholic fatty liver disease (NAFLD) and/or the symptom associated thereto.

### Claim 18 (depends on 18)

The method of claim 18, wherein the synthetic peptide comprises (i) an analogue comprising the amino acid sequence set forth in SEQ ID NO:3 and (ii) a recognition and/or localization peptide comprising the amino acid sequence set forth in SEQ ID NO:8.

### Claim 19 (depends on 18)

The method of claim 18, wherein the synthetic peptide comprises the amino acid sequence set forth in SEQ NO:14.

### Claim 20

A synthetic peptide comprising an analogue of VDAC1-derived peptide, the VDAC 1-derived peptide is capable of inducing apoptosis in cancerous cells and consists of 5-26 contiguous amino acids, wherein the analogue comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:5 and is partially inverso modified.