Targeting monomers and polymers having targeting blocks

Patent metadata

Field	Value
Publication number	US-9415113-B2
Application number	US-201013510279-A
Country	US
Kind code	B2
Filing date	Nov 17, 2010
Priority date	Nov 18, 2009
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

Provided herein are monomers incorporating folate or other targeting agent, polymers prepared therefrom, polymers prepared therefrom having a therapeutic agent covalently coupled thereto, as well as micelles and therapeutic compositions thereof.

First claim

What is claimed is:

1. A monomer of Formula M1

wherein
M 1 and M 2 are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, and substituted carbonyl, provided, however, M 1 and M 2 are not each selected from the group consisting of aryl, heteroaryl, and heterosubstituted carbonyl;
M 3 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or substituted carbonyl, and
M 4 is —C(O)OM 40 , —C(O)SM 40 , —C(O)NM 40 M 41 , —Ar-M 40 or -Het-M 40 , Ar is arylene, Het is heteroarylene, M 41 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterohydrocarbyl, substituted heterohydrocarbyl, or heterocyclo, and M 40 contains, as a terminal moiety, a targeting moiety selected from the group consisting of folate and folate analogs, provided M 3 and M 4 are not each selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, and heterosubstituted carbonyl.

2. The monomer of claim 1 wherein M 3 is hydrogen, methyl, ethyl, or propyl.

3. The monomer of claim 1 wherein M 40 is a substituted hydrocarbyl or a substituted heterohydrocarbyl containing the terminal targeting moiety.

4. The monomer of claim 1 wherein M 3 is hydrogen, methyl, ethyl, or propyl; and M 40 is a substituted hydrocarbyl or a substituted heterohydrocarbyl containing the terminal targeting moiety.

5. The monomer of claim 1 wherein M 3 is hydrogen, methyl, ethyl, or propyl; and M 4 is —C(O)OM 40 , —C(O)SM 40 , or —C(O)NM 40 M 41 .

6. The monomer of claim 1 wherein M 40 contains, as the terminal targeting moiety, a moiety having the formula

wherein the symbol, , designates the point of attachment of the targeting moiety to the remainder of M 40 , T 4 is hydroxy, optionally substituted alkoxy, or amino, T 5 is hydrogen or alkyl, and T 6 is hydrogen or optionally substituted alkyl.

7. A monomer of Formula M10

wherein M 3 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or substituted carbonyl; Y is a bond or a linking group selected from the group consisting of hydrocarbylene, substituted hydrocarbylene, heterohydrocarbyl, and substituted heterohydrocarbyl; T 4 is hydroxy, optionally substituted alkoxy, or amino; T 5 is hydrogen or alkyl, T 6 is hydrogen, alkyl, substituted alkyl, heterohydrocarbyl, or substituted heterohydrocarbyl; Z is —C(O)O—, —C(O)S—, —C(O)N(M 41 )-, —Ar-M 49 - or Het-M 49 -; Ar is arylene; Het is heteroarylene; M 41 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterohydrocarbyl, substituted heterohydrocarbyl, or heterocyclo; M 49 is oxygen, sulfur, or —N(M 50 )-; and M 50 is hydrogen, hydrocarbyl or substituted hydrocarbyl.

8. The monomer of claim 7 wherein M 3 is hydrogen, methyl, ethyl, or propyl, T 4 is hydroxy, and T 5 and T 6 are hydrogen.

9. The monomer of claim 7 wherein M 3 and T 6 are independently hydrogen, methyl, ethyl, or propyl; Z is —C(O)O—, —C(O)S—, or —C(O)N(M 41 )-; and M 41 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterohydrocarbyl, substituted heterohydrocarbyl, or heterocyclo.

10. The monomer of claim 7 wherein Y is alkylene or (poly)alkylene oxide.

11. The monomer of claim 7 wherein M 3 and T 6 are independently hydrogen, methyl, ethyl, or propyl, Z is —C(O)O—, —C(O)S—, or —C(O)N(M 41 )-; Y is alkylene or (poly)alkylene oxide; and M 41 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterohydrocarbyl, substituted heterohydrocarbyl, or heterocyclo.

12. The monomer of claim 7 wherein Z is —C(O)O— or —C(O)S— and the is of Formula M11 or M12

wherein M 3 is hydrogen, methyl, ethyl, or propyl, Y is a linking group selected from the group consisting of hydrocarbylene, substituted hydrocarbylene, heterohydrocarbyl, and substituted heterohydrocarbyl; T 4 is hydroxy, optionally substituted alkoxy, or amino; T 5 is hydrogen or alkyl, and T 6 is hydrogen, alkyl or substituted alkyl.

13. The monomer of claim 5 , wherein M 40 is a substituted hydrocarbyl or a substituted heterohydrocarbyl containing the terminal targeting moiety.

Assignees

• Monahan Sean D
• Johnson Paul H
• Declue Michael S
• De Priyadarsi
• Gall Anna S
• Stayton Patrick S
• Hoffman Allan S
• Diab Charbel
• Univ Washington
• Phaserx Inc

Inventors

• Monahan Sean D
• Johnson Paul H
• Declue Michael S
• De Priyadarsi
• Gall Anna S
• Stayton Patrick S
• Hoffman Allan S
• Diab Charbel

Classifications

• A61K47/48146

  Human Necessities · mapped topic

• A61K47/48238

  Human Necessities · mapped topic

• A61K47/48107

  Human Necessities · mapped topic

• A61K47/48176 Primary

  Human Necessities · mapped topic

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title