Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same

• US 8,110,651 B2
• Filed: 01/12/2009
• Issued: 02/07/2012
• Est. Priority Date: 01/11/2008
• Status: Active Grant

• Current Assignee: Serina Therapeutics, Inc.
• Original Assignee: Serina Therapeutics, Inc.
• Inventors: Yoon, Kunsang, Harris, J. Milton, Bentley, Michael David
• Primary Examiner(s): Truong, Duc
• Application Number:
  US12/744,472
• Publication Number:
  US 20110009594A1
• Time in Patent Office: 1,121 Days
• Field of Search: 528/373, 528/321, 528/403
• US Class Current: 528/321
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: C08G 73/0233 Polyamines derived from (poly)oxazolines, (poly)oxazines or having pendant acyl groups
• CPC Class Codes: C08G 73/028 Polyamidoamines

Abstract

The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Claims

1. A heterofunctional polyoxazoline derivative having the general structure:

R₁—

{[N(COX)CH₂CH₂]_O-[n(COR₂)CH₂—

CH₂)]_a}—

S—

U—

W

wherein;

R₁ is an initiating group;

R₂ is an unsubstituted or substituted alkyl, an unsubstituted or substituted alkenyl, an unsubstituted or substituted aralkyl or an unsubstituted or substituted heterocyclylalkyl group;

U is a linking group;

X is a pendent moiety containing a first functional group;

W comprises a moiety bearing a second functional group;

a is random which indicates a random copolymer or block which indicates a block copolymer;

o is an integer selected from 1-50;

n is an integer selected from 0-1000; and

wherein the first and second functional groups are chemically orthogonal to one another.

2. The heterofunctional polyoxazoline derivative of claim 1 wherein the first and second functional group are each independently an alkyne, an amine, an oxyamine, an aldehyde, a ketone, an acetal, a ketal, an ester, a carboxylic acid, an activated carboxylic acid, an active carbonate, a chloroformate, an alcohol, an azide, a vinyl sulfone, a maleimide or orthopyridyl disulfide.

3. The heterofunctional polyoxazoline derivative of claim 2 wherein the carboxylic acid is a negatively charged species and the amine is a positively charged species.

4. The heterofunctional polyoxazoline derivative of claim 1 wherein R₁ is a hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aralkyl group.

5. The heterofunctional polyoxazoline derivative of claim 1 wherein U is an alkylene linking group.

6. The heterofunctional polyoxazoline derivative of claim 5 wherein W is —

CO₂H or —

NH₂.

7. The heterofunctional polyoxazoline derivative of claim 1 linked to at least one a target molecule to form a target molecule-POZ conjugate.

8. The heterofunctional polyoxazoline derivative of claim 7 wherein the at least one target molecule is linked to the polyoxazoline derivative through at least one of the first or second functional groups.

9. The heterofunctional polyoxazoline derivative of claim 8 wherein the at least one target molecule is a therapeutic moiety, a diagnostic moiety or a targeting moiety and the target molecule-POZ conjugate contains a therapeutic moiety and a targeting moiety, a diagnostic moiety and a targeting moiety or a diagnostic moiety, a therapeutic moiety and a targeting moiety.