Conjugate and cancer therapeutic agent

Patent metadata

Field	Value
Publication number	US-12433857-B2
Application number	US-202017605027-A
Country	US
Kind code	B2
Filing date	Apr 23, 2020
Priority date	Apr 24, 2019
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

A conjugate is provided in which a deferoxamine-type compound, which is at least one compound selected from the group consisting of deferoxamine or an ion or salt thereof, and a derivative thereof, and a biocompatible polymer are conjugated, where the biocompatible polymer contains a first biocompatible polymer chain and a second biocompatible polymer chain that is different from the first biocompatible polymer chain.

First claim

What is claimed is:

1. A mixed drug comprising ascorbic acid and a conjugate in which a deferoxamine-type compound, which is at least one compound selected from the group consisting of deferoxamine or an ion or salt thereof, and a derivative thereof, and a biocompatible polymer are conjugated,
wherein the biocompatible polymer contains a first biocompatible polymer chain and a second biocompatible polymer chain that is different from the first biocompatible polymer chain,
wherein the second biocompatible polymer chain is a polyamino acid,
the first biocompatible polymer chain is polyethylene glycol, and
the conjugate includes a structure having Formula (1):
A-L-B   (1)

wherein A represents the first biocompatible polymer chain; L represents a linker part; and B represents the second biocompatible polymer chain, and
wherein the conjugate includes a structure having Formula (1-2):

wherein 1 is an integer of 1 to 1,500, B represents the second biocompatible polymer chain and includes a repeating structure represented by formula (b2-1), or a repeating structure represented by formula (b1-1) and a repeating structure represented by formula (b2-1),

wherein R 11 represents an amino acid side chain; R 12 is a group obtained by conjugating a carboxyl group in an aspartic acid side chain represented by —CH 2 —COOH or a carboxyl group in a glutamic acid side chain represented by —CH 2 —CH 2 —COOH to the deferoxamine-type compound; and n 1 represents the total number of (b1-1) and (b2-1) structures, n 1 is an integer of 1 to 1,000, m 1 is an integer of 1 to 1,000, m 1 ≤n 1 , when n 1 −m 1 is 2 or more, a plurality of R 11 's may be the same as or different from each other, and when m 1 is 2 or more, a plurality of R 12 's may be the same as or different from each other.

2. The mixed drug according to claim 1 , wherein the conjugate has a number average molecular weight of 2,000 to 200,000.

3. A method for treating a cancer, the method comprising:
administering a mixed drug comprising ascorbic acid and a conjugate to a subject in need of treatment,
wherein the conjugate is a conjugate in which a deferoxamine-type compound, which is at least one compound selected from the group consisting of deferoxamine or an ion or salt thereof, and a derivative thereof, and a biocompatible polymer are conjugated,
wherein the biocompatible polymer contains a first biocompatible polymer chain and a second biocompatible polymer chain that is different from the first biocompatible polymer chain,
wherein the second biocompatible polymer chain is a polyamino acid,
the first biocompatible polymer chain is polyethylene glycol, and
the conjugate includes a structure having Formula (1):
A-L-B   (1)

wherein A represents the first biocompatible polymer chain; L represents a linker part; and B represents the second biocompatible polymer chain, and
wherein the conjugate includes a structure having Formula (1-2):

wherein 1 is an integer of 1 to 1,500, B represents the second biocompatible polymer chain and includes a repeating structure represented by formula (b2-1), or a repeating structure represented by formula (b1-1) and a repeating structure represented by formula (b2-1),

wherein R 11 represents an amino acid side chain; R 12 is a group obtained by conjugating a carboxyl group in an aspartic acid side chain represented by —CH 2 —COOH or a carboxyl group in a glutamic acid side chain represented by —CH 2 —CH 2 —COOH to the deferoxamine-type compound; and n 1 represents the total number of (b1-1) and (b2-1) structures, n 1 is an integer of 1 to 1,000, m 1 is an integer of 1 to 1,000, m 1 ≤n 1 , when n 1 −m 1 is 2 or more, a plurality of R 11 's may be the same as or different from each other, and when m 1 is 2 or more, a plurality of R 12 's may be the same as or different from each other.

Assignees

• Tokyo Inst Tech
• Sbi Pharmaceuticals Co Ltd

Inventors

• Nishiyama Nobuhiro
• Nomoto Takahiro
• KOHMOTO Kana
• Takemoto Hiroyasu
• Matsui Makoto

Classifications

• A61K47/645

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K31/16 Primary

  Amides, e.g. hydroxamic acids · CPC title