Zwitterionic polymers with therapeutic moieties

Patent metadata

Field	Value
Publication number	US-10632206-B2
Application number	US-201615198372-A
Country	US
Kind code	B2
Filing date	Jun 30, 2016
Priority date	Dec 12, 2008
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

The invention generally relates to zwitterionic polymers (including zwitterionic copolymers), such as polymethacrylic structures, with pendent functional moieties, such as therapeutic or biologic moieties. More particularly, the invention relates to phosphorylcholine-substituted methacrylic polymers prepared by free radical polymerization and click chemistry, for example, and compositions and products comprising same, as well as related methods and uses of the compositions, for example, as biological or therapeutic agents and in drug delivery thereof.

First claim

The invention claimed is:

1. A co-polymer comprising the structural unit of:

wherein
each of R 1 and R 3 is independently a hydrogen, alkyl, or halogen;
each of R 2 and R 4 is independently a hydrogen, (C 1 -C 15 ) alkyl, (C 1 -C 15 ) alkyloxy, or halogen;
R Z is a group comprising a zwitterionic moiety;
m is an integer from 1 to about 500;
n is an integer from 1 to about 100;
L q is a linking group;
R x-y is selected from the group consisting of:

L A is a linking group; and
A is an agent having a biological activity, wherein A is a protein, an antibody, an enzyme, or a small molecule or polymeric agent for treating cancer.

2. The co-polymer of claim 1 , wherein L A is a single bond, or a bivalent alkyl, alkyloxy, or aryl group.

3. The co-polymer of claim 1 , wherein L A comprises the moiety of

wherein R AL is selected from, H, —OH, halogen, alkyl groups, and oxyalkyl.

4. The co-polymer of claim 1 , wherein A is doxorubicin:

5. The co-polymer of claim 1 , wherein the ratio of zwitterionic moiety:A is from about 2:1 to about 10:1.

6. A co-polymer comprising the structure of:

wherein
each of R 1 and R 3 is independently a hydrogen, alkyl, or halogen;
each of R 2 and R 4 is independently a hydrogen, (C 1 -C 15 ) alkyl, (C 1 -C 15 ) alkyloxy, or halogen;
R Z is a group comprising a zwitterionic moiety;
m is an integer from 1 to about 500;
n is an integer from 1 to about 100;
L q is a linking group;
R x-y is selected from the group consisting of:

L A is a linking group;
A is an agent having a biological activity, wherein A is a protein, an antibody, an enzyme, or a small molecule or polymeric agent for treating cancer;
L T is a linking group; and
T is a targeting moiety towards a biological target to which A has biological activity, wherein T is selected from the group consisting of an antibody, a protein, an aptamer, and a small molecule comprising a folate moiety.

7. The co-polymer of claim 6 , wherein, L T comprises an amide moiety.

8. The co-polymer of claim 6 , wherein the zwitterionic moiety comprises one or more of phosphorylcholine and sulfobetaine.

9. The co-polymer of claim 6 , wherein R Z comprises a linker group L Z covalently attached to the ester group and the zwitterionic moiety
-L Z -zwitterion.

10. The co-polymer of claim 9 , wherein L Z is a single bond, a bivalent alkyl, alkyloxy, or aryl group.

11. The co-polymer of claim 6 , wherein each of R 1 , R 2 , R 3 , and R 4 is independently selected from the group consisting of hydrogen, methyl, ethyl, and F.

12. The co-polymer of claim 6 , wherein A is a therapeutic agent for treating cancer.

13. The co-polymer of claim 12 , wherein A is selected from campothecin, irinotecan, and SN-38.

14. The co-polymer of claim 6 , wherein the ratio of zwitterionic moiety:A is from about 2:1 to about 10:1.

Assignees

• Univ Massachusetts

Inventors

• Emrick Todd
• Chen Xiangji
• Page Samantha

Classifications

• C08F8/30

  Introducing nitrogen atoms or nitrogen-containing groups · CPC title

• C08F2438/01

  Atom Transfer Radical Polymerization [ATRP] or reverse ATRP · CPC title

• C08F230/02

  containing phosphorus · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• C08F238/00

  Copolymers of compounds having one or more carbon-to-carbon triple bonds · CPC title