IP Library Granted Patent US 9,790,324
Granted Patent B2
US 9,790,324 · App. 14/499,354 · Granted Oct 17, 2017

Functionalized polymers

Inventor: Marek Kwiatkowski (Uppsala, SE)
C08G65/48A61K47/48215
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Quick Facts
Patent No.
US 9,790,324
App. No.
14/499,354
Granted
Oct 17, 2017
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 (47)

1. A compound 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), wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da;

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;

M is a protected group that when deprotected is reactive with a biologically active molecule, a group reactive with a biologically active molecule;

R is absent or selected from the group consisting of: hydrogen, a protecting group, a hydrophobic separation handle, or an activating group;

R 1 is absent or a hydrophobic separation handle;

wherein when M is a protected group that when deprotected is reactive with a biologically active molecule, then R is a protecting group or a hydrophobic separation handle;

wherein when M is a group reactive with a biologically active molecule, R is absent, hydrogen, or an activating group; and

wherein only one of R, R 1 , and G can be a hydrophobic separation handle.

2. The compound of claim 1 , wherein the polymer has from 2 to 100 termini.

3. The compound of claim 1 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (1).

4. The compound of claim 1 , wherein the polymer backbone has two termini.

5. The compound of claim 4 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (1).

6. The compound of claim 4 , wherein both termini of the polymer backbone are covalently bonded to the structure of formula (1).

7. The compound of claim 1 , wherein said group reactive with a biologically active molecule is selected from the group consisting of: hydroxyl, amine, thiol, carboxyl, aldehyde, glyoxal, dione, alkenyl, alkynyl, alkedienyl, azide, acrylamide, vinyl sulfone, hydrazide, aminoxy, maleimide, dithiopyridine, iodoacetamide.

8. The compound 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.

9. The compound of claim 1 , wherein G is a substituted or unsubstituted trityloxy.

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

11. The compound claim 1 , wherein R is selected from the group consisting of: trityl, monoalkoxytrityl, dialkoxytrityl, pixyl, alkoxypixyl, fluorenylmethyloxycarbonyl, trifluoroacetyl, acetal, and cyclic acetal.

12. The compound of claim 1 , wherein said group reactive with a biologically active molecule is carboxyl and R is absent or selected from the group consisting of:

chlorotrityl, trityl, N-hydroxysuccinimidyl, p-nitrophenyl, pentachlorophenyl, and an unsubstituted C 1 -C 18 alkyl.

13. A preparation comprising a compound comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one termini 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), wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da;

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;

M is a protected group that when deprotected is reactive with a biologically active molecule, a group reactive with a biologically active molecule;

R is absent or selected from the group consisting of: hydrogen, a protecting group, a hydrophobic separation handle, or an activating group;

R 1 is absent or a hydrophobic separation handle;

provided that only one of R and R 1 is a hydrophobic separation handle or the hydrophobicity of one of R or R 1 is higher than the other;

wherein when M is a protected group that when deprotected is reactive with a biologically active molecule, then R is a protecting group or a hydrophobic separation handle;

wherein when M is a group reactive with a biologically active molecule, R is absent, hydrogen, or an activating group;

wherein said preparation comprises at least 50% by weight of said compound; and

wherein only one of R, R 1 , and G can be a hydrophobic separation handle.

14. The preparation of claim 13 , wherein the compound is essentially pure.

Assignments (4)
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 Oct 9, 2014
From: KWIATKOWSKI, MAREK
To: QUIAPEG AB
Reel/Frame 033924/0428 →
Priority Claims (1)
SE 1001187 · Dec 13, 2010 · national
Continuity (2)
Continuation 13324872 · Dec 13, 2011
Related Publication 20150232615A1 · Aug 20, 2015