IP Library Granted Patent US 10,781,286
Granted Patent B2
US 10,781,286 · App. 16/186,900 · Granted Sep 22, 2020

Functionalized polymers

Inventor: Marek Kwiatkowski (Uppsala, SE)
Assignee: QuiaPEG Pharmaceuticals AB
C08G65/48A61K47/60C07F9/091C07F9/094C07F9/1651C07F9/1653C07F9/2408C07F9/2458C07F9/2475C07F9/572C07F9/6561C07F9/65515C08G81/00
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Quick Facts
Patent No.
US 10,781,286
App. No.
16/186,900
Granted
Sep 22, 2020
Kind
B2
Abstract

This document relates to functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such functionalized polymers.

Claims (61)

1. A conjugate, or a pharmaceutically acceptable salt thereof, comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one terminus covalently bonded to a structure of formula (1):

or a salt thereof,

wherein:

A is the point of covalent bonding to the terminus of the polymer backbone, wherein the polymer backbone is poly(ethylene glycol);

E is O;

K is selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G is selected from the group consisting of: hydrogen, alkoxy, and a hydrophobic separation handle;

Z 1 is O;

Z 2 is O;

L is selected from the group consisting of: a divalent radical of a nucleoside, alkylene, alkyleneoxyalkylene, oligomeric alkyleneoxyalkylene, and unsubstituted and substituted arylene;

R 1 is absent or a hydrophobic separation handle;

M is a biologically active molecule; and

R is absent.

2. The conjugate of claim 1 , wherein the poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da.

3. The conjugate of claim 1 , wherein K is selected from the group consisting of: methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, and hexylene, or a residue from diethylene glycol, triethylene glycol, tetraethylene glycol or hexaethylene glycol.

4. The conjugate of claim 1 , wherein G is a substituted or unsubstituted trityloxy.

5. The conjugate of claim 1 , wherein L is a substituted or unsubstituted C 1 -C 12 alkylene.

6. The conjugate of claim 1 , wherein said biologically active molecule is selected from the group consisting of enzymes, peptides, polypeptides, nucleotides, oligonucleotides, polynucleotides, and therapeutic agents having a molecular weight of less than 1000 g/mol.

7. A conjugate, or a pharmaceutically acceptable salt thereof, comprising a compound of formula (2):

or a salt form thereof,

wherein:

polymer is a linear poly(ethylene glycol), wherein each linking group is bonded at a different terminus of said poly(ethylene glycol);

E is O;

E 1 is O or S;

K and K 1 are independently selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G and G 1 are independently absent or are selected from the group consisting of: alkoxy and a hydrophobic separation handle;

Z 1 is O;

Z 2 is O;

Z 3 and Z 4 are independently selected from 0 and NH, wherein no more than one of Z 3 and Z 4 is NH;

L is a divalent radical of an alkylene;

L 1 is selected from the group consisting of: a divalent radical of a nucleoside, alkylene, alkyleneoxyalkylene, oligomeric alkyleneoxyalkylene, and unsubstituted and substituted arylene;

R and R 1 are absent;

M is a biologically active molecule; and

M 1 is a biologically active molecule.

8. The conjugate of claim 7 , wherein the poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da.

9. The conjugate of claim 7 , wherein K or K 1 is independently selected from the group consisting of: methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, and hexylene, or a residue from diethylene glycol, triethylene glycol, tetraethylene glycol or hexaethylene glycol.

10. The conjugate of claim 7 , wherein G or G 1 is independently a substituted or unsubstituted trityloxy.

11. The conjugate of claim 7 , wherein L or L 1 is independently a substituted or unsubstituted C 1 -C 12 alkylene.

12. The conjugate of claim 1 , wherein said biologically active molecule is selected from the group consisting of enzymes, peptides, polypeptides, nucleotides, oligonucleotides, polynucleotides, and therapeutic agents having a molecular weight of less than 1000 g/mol.

13. A conjugate, or a pharmaceutically acceptable salt thereof, comprising a compound of formula (3):

or a salt form thereof,

wherein:

polymer is a linear poly(ethylene glycol), wherein M 2 and the phosphonate-derived functional group are bonded at a different terminus of said poly(ethylene glycol);

E is O;

E 1 is O or S;

K is selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G is selected from the group consisting of: hydrogen, alkoxy, and a hydrophobic separation handle;

Z 1 is O;

Z 2 is O;

L is selected from the group consisting of: a divalent radical of nucleoside, alkylene, alkyleneoxyalkylene, oligomeric alkyleneoxyalkylene, and unsubstituted and substituted arylene;

M is a biologically active molecule;

M 2 is selected from O, S or NH; and

R is absent; and

R 2 is hydrogen or a protecting group.

14. The conjugate of claim 13 , wherein the poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da.

15. The conjugate of claim 13 , wherein K is selected from the group consisting of: methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, and hexylene, or a residue from diethylene glycol, triethylene glycol, tetraethylene glycol or hexaethylene glycol.

16. The conjugate of claim 13 , wherein G is a substituted or unsubstituted trityloxy.

17. The conjugate of claim 16 , wherein G is selected from a monoalkoxy substituted trityloxy group or dialkoxy substituted trityloxy group.

18. The conjugate of claim 13 , wherein L is a substituted or unsubstituted C 1 -C 12 alkylene.

19. The conjugate of claim 13 , wherein R 2 is selected from the group consisting of trityl, monoalkoxytrityl, dialkoxytrityl, pixyl, alkoxypixyl, fluorenylmethyloxycarbonyl, alkylcarboxyl, benzoyl, tetrahydropyranyl, methyl.

20. The conjugate of claim 13 , wherein said biologically active molecule is selected from the group consisting of enzymes, peptides, polypeptides, nucleotides, oligonucleotides, polynucleotides, and therapeutic agents having a molecular weight of less than 1000 g/mol.

Assignments (6)
LIEN Recorded Nov 29, 2023
From: QUIAPEG AB
To: FISH & RICHARDSON PC
Reel/Frame 065714/0116 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2020
From: KWIATKOWSKI, MAREK
To: QUIAPEG AB
Reel/Frame 052275/0593 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2020
From: KWIATKOWSKI, MAREK
To: QUIAPEG PHARMACEUTICALS AB
Reel/Frame 052276/0590 →
CHANGE OF NAME Recorded Mar 31, 2020
From: QUIAPEG AB
To: QUIAPEG PHARMACEUTICALS AB
Reel/Frame 052279/0732 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 14, 2019
From: KWIATKOWSKI, MAREK
To: QUIAPEG AB
Reel/Frame 047987/0764 →
CHANGE OF NAME Recorded Jan 14, 2019
From: QUIAPEG AB
To: QUIAPEG PHARMACEUTICALS AB
Reel/Frame 048069/0452 →
Priority Claims (1)
SE 1001187 · Dec 13, 2010 · national
Continuity (4)
Continuation 15727706 · Oct 9, 2017
Continuation 14499354 · Sep 29, 2014
Continuation 13324872 · Dec 13, 2011
Related Publication 20190315918A1 · Oct 17, 2019