Conjugate of bio-related substance and block polymer, and block polymer derivative for obtaining said conjugate

Patent metadata

Field	Value
Publication number	US-12448488-B2
Application number	US-201917603275-A
Country	US
Kind code	B2
Filing date	Apr 15, 2019
Priority date	Apr 15, 2019
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

The invention provides a modified bio-related substance that shows further prolonged half-life in blood and further improved stability in the blood of living organisms. In particular, the invention provides a conjugate of a block polymer and a bio-related substance, which conjugate is represented by the following formula (I), wherein each symbol is as described herein.

First claim

The invention claimed is:

1. A conjugate of a block polymer and a bio-related substance, which is represented by the following formula (1):

wherein A is a bio-related substance selected from the group consisting of a cytokine, a hormone, an enzyme, an antibody, and a nucleic acid, L 1 , L 2 , L 3 are each independently a single bond or a divalent linker, Q is a residue of a compound having 2 or 3 active hydrogens, m is 10-1400, n is 2-100, x is 1 or 2, R is a hydrogen atom or an acyl group, p is 1 or 2, and y is 1-40.

2. The conjugate according to claim 1 , wherein, in the formula (1), y is 1.

3. The conjugate according to claim 2 , wherein, in the formula (1), m is 40-1200 and n is 5-50.

4. The conjugate according to claim 3 , wherein, in the formula (1), Q is a residue of a compound selected from the group consisting of ethylene glycol, glycerol, lysine, aspartic acid and glutamic acid.

5. The conjugate according to claim 4 , wherein, in the formula (1), L 1 , L 2 , L 3 are each independently selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol, an oxyme bond, and an alkylene group optionally containing one or more kinds selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol and an oxyme bond.

6. The conjugate according to claim 2 , wherein, in the formula (1), Q is a residue of a compound selected from the group consisting of ethylene glycol, glycerol, lysine, aspartic acid and glutamic acid.

7. The conjugate according to claim 2 , wherein, in the formula (1), L 1 , L 2 , L 3 are each independently selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol, an oxyme bond, and an alkylene group optionally containing one or more kinds selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol and an oxyme bond.

8. The conjugate according to claim 1 , wherein, in the formula (1), m is 40-1200 and n is 5-50.

9. The conjugate according to claim 1 , wherein, in the formula (1), Q is a residue of a compound selected from the group consisting of ethylene glycol, glycerol, lysine, aspartic acid and glutamic acid.

10. The conjugate according to claim 1 , wherein, in the formula (1), L 1 , L 2 , L 3 are each independently selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol, an oxyme bond, and an alkylene group optionally containing one or more kinds selected from the group consisting of a single bond, a phenylene group, an amide bond, an ether bond, a thioether bond, a urethane bond, a secondary amino group, a carbonyl group, a urea bond, a triazine group, a maleimide group added with thiol and an oxyme bond.

Assignees

• Nof Corp
• Univ Degli Studi Padova

Inventors

• Yoshioka Hiroki
• Hirai Midori
• Kamiya Masaki
• Pasut Gianfranco

Classifications

• A61K38/27

  Growth hormone [GH], i.e. somatotropin · CPC title

• A61K47/595

  Polyamides, e.g. nylon (polyamino acids A61K47/62) · CPC title

• A61K47/54

  the modifying agent being an organic compound · CPC title

• C08G69/40

  Polyamides containing oxygen in the form of ether groups (C08G69/12, C08G69/32 take precedence) · CPC title

• C08G69/10

  Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)} · CPC title