# US 12,595,289 B2 · Therapeutic agent for breast cancer comprising BIG3-PHB2 interaction-inhibiting peptide derived from PHB2

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

- Number: US 12,595,289 B2
- Document ID: US12595289B2
- Status: Granted
- Kind: B2
- Application number: 17/297,986
- Filed: 2019-11-28
- Published: 2022-03-31
- Granted: 2026-04-07
- Earliest claimed: 2018-11-30
- Assignees: Tokushima University; Oncotherapy Science, Inc.
- Applicants: Tokushima University; Oncotherapy Science, Inc.
- Inventors: Toyomasa Katagiri; Tetsuro Yoshimaru; Akira Otaka; Takashi Miyamoto; Yasuhide Okamoto
- Web page: https://patentgrep.com/patent/US12595289B2

## CPC

- C07K 14/4703: {Inhibitors; Suppressors}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE}
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- 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: 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 provides peptides containing the BIG3 polypeptide-binding site in a PHB2 polypeptide, which inhibit the binding between a PHB2 polypeptide and a BIG3 polypeptide, and pharmaceutical compositions containing the peptide. The peptides of the present invention have the ability to bind not to PHB2, whose expression is found in organs throughout the human body, but to BIG3, which is a protein highly expressed specifically in particularly estrogen receptor-positive cancer, and have excellent growth suppressive effects on BIG3-positive cancer cells. Accordingly, the peptides of the present invention are useful as therapeutic agents for breast cancer which can avoid expression of side effects.

## Claims

### Claim 1

A cyclic peptide, comprising a site binding to a BIG3 polypeptide in a PHB2 polypeptide, wherein the cyclic peptide inhibits the binding between the PHB2 polypeptide and the BIG3 polypeptide, wherein the cyclic peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 25, 123, 124, 106 to 108, and 115 to 117, and wherein the cyclic peptide comprises a single intramolecular crosslink between the two cysteine residues.

### Claim 2 (depends on 1)

The cyclic peptide of claim 1, wherein the cyclic peptide has either or both of the following properties (i) and (ii):
(i) suppressing growth of BIG3-positive cells; and
(ii) promoting phosphorylation of a serine residue in the PHB2 polypeptide in BIG3-positive cells.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising: at least one ingredient selected from the group consisting of one or more of the cyclic peptides of claim 1, and a pharmaceutically acceptable salt(s) of the peptide(s); and a pharmaceutically acceptable carrier.

### Claim 4 (depends on 1)

The cyclic peptide of claim 1, wherein the single intramolecular crosslink is a hexafluorobenzene crosslink.

### Claim 5 (depends on 1)

The cyclic peptide of claim 1, wherein the single intramolecular crosslink is a decafluorobiphenyl crosslink.

### Claim 6 (depends on 1)

The cyclic peptide of claim 1, wherein the single intramolecular crosslink is a disulfide crosslink.